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Alzheimer Disease - New Drugs, Markets and Companies

  • ID: 4748164
  • Report
  • May 2020
  • Region: Global
  • 559 Pages
  • Jain PharmaBiotech
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Alzheimer's disease remains a challenge in management. With nearly 8 million sufferers from this condition in the seven major markets of the world and anticipated increases in the future. Considerable research is in progress to understand the pathomechanism of the disease and find a cure. The only drugs approved currently are acetylcholinesterase inhibitors but they do not correct the basic pathology of the disease, beta amyloid deposits and neurofibrillary tangles. Several new approaches emphasize neuroprotection as well.

Early diagnosis of Alzheimer's disease is an important first step in management. Several biomarkers in cerebrospinal fluid, blood and urine can detect the disease. They provide a valuable aid to the clinical examination and neuropsychological testing which are the main diagnostic methods supplemented by brain imaging. Genotyping, particularly of ApoE gene alleles is also useful in the evaluation of cases and planning management.

The current management of Alzheimer's disease is reviewed and it involves a multidisciplinary approach. Acetylcholinesterase inhibitors are mostly asymptomatic treatment but some claims are made about a neuroprotective effect. Currently the only approved neuroprotective therapy in is memantine. Management of these patients also require neuroleptics for aggressive behavior and antidepressants. There is an emphasis on early detection at the stage of mild cognitive impairment and early institution of neuroprotective measures. The value of mental exercise in delaying the onset of Alzheimer's disease is being recognized.

Research in Alzheimer's disease still aims at elucidating the basic pathomechanisms. Animal models are important for research, particularly in testing some of the potential therapeutic approaches. There is considerable research in progress at the various centers, some of which is funded by the National Institute of Aging of the National Institutes of Health.

Over 300 different compounds are at various stages of development for the treatment of Alzheimer's disease. These are classified and described. There are non-pharmacological approaches such as vagal nerve stimulation and cerebrospinal fluid shunting, which are in clinical trials. Ongoing as well as discontinued clinical trials of AD are tabulated.

Alzheimer's disease market in the seven major markets is analyzed for the year 2019. Several new therapies are expected to be in the market and the shares of various types of approaches are estimated for the future up to the year 2029. As a background to the markets, pharmacoeconomic aspects of care of Alzheimer disease patients and patterns of practice are reviewed in the seven major markets.

Profiles of 117 companies involved in developing diagnostics and therapeutics for Alzheimer's disease are presented along with 89 collaborations. The bibliography contains over 900 publications that are cited in the report.The report is supplemented with 48 tables and 27 figures.

The report contains information on the following:

  • Clinical features, epidemiology, and pathology of Alzheimer disease
  • Diagnostic procedures for Alzheimer's disease
  • Management of Alzheimer's disease
  • Research in Alzheimer's disease
  • Drug discovery and development for Alzheimer's disease
  • Marketing and financial aspects of Alzheimer's disease
  • Companies
Note: Product cover images may vary from those shown
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0. Executive Summary

1. Clinical Features, Epidemiology and Pathology
Historical aspects
Clinical features of Alzheimer disease
Seven stages of Alzheimer disease
AD as a terminal illness
Detection of AD in the preclinical phase
Differentiation of AD from other dementias
Differentiation of AD from non-dementing disorders
Cerebral insufficiency and AD
Memory deficits and preclinical AD
Sleep disorders and AD
Circadian rhythms and sleep in AD
Mild cognitive impairment
Evolution of diagnostic criteria of AD
Revised criteria for the clinical diagnosis of AD
Epidemiology of aging
Epidemiology of dementia
Epidemiology of AD
Prevalence of AD according to age
Mortality in AD
Pathophysiology of AD
Cerebral atrophy and neuronal loss
Neuritic plaques and neurofibrillary tangles
See-through 3D imaging of the AD brain
Sp proteins as biomarkers of neuronal death in AD
Role of tau in the pathogenesis of AD
RNA-binding proteins and AD
Amyloid precursor protein
APP intracellular domain
Relation of APP mutations to CNS disorders
Relation of APP to Aβ deposits and pathogenesis of AD
Role of neprilysin in Aβ degradation
Role of secretases in amyloid cascade
Role of exosomal proteins
Role of nicastrin
Neurotoxicity of Aβ deposits
Aβ production and clearance
Aβ-mediated synaptic and cognitive deficits
Dysfunction of TGF-β signaling accelerates Aβ deposition
Interaction of Aβ with neuron-specific Na+/K+-ATPase α3 subunit
Relation of Aβ deposits to synaptic activity
Role of TMP21 in presenilin complexes and Aβ formation
Role of Aβ dimers in the pathogenesis of AD
Role of dsDNA breaks in neurodegeneration due to Aß
Structure–neurotoxicity relationships of Aβ oligomers
Sequence of events in neurotoxicity of Aβ
AD as an ion channel disorder
Neural thread protein
Loss of synaptic proteins
AD and Down syndrome
AD and age-related macular degeneration
Blood-brain barrier in AD
Blood vessel damage in AD
Fibrinogen-induced loss of synapses
Loss of serotonin 1A receptors in the brain
Myelin hypothesis of AD
Overlapping pathologies of AD and Parkinson disease
Factors in pathogenesis of AD
Astrocytes and AD
Axonal transport failure in AD
Cell-cycle hypothesis
Chronic heart failure link with AD
Creatine and AD
Disturbances in brain metabolism in early AD
Disturbance of lipid metabolism in the brain
DENN/MADD expression and enhanced pro-apoptotic signaling in AD
Dopamine and AD
Functioning role of genes in pathomechanism of AD
Gonadotrophins and AD
Glutamate transport dysfunction in AD
Herpes simplex virus type 1 and AD
Innate immune system and AD
Insulin, diabetes and AD
Mechanisms underlying cognitive deficits in AD
Microglia and AD
Monoamine oxidase and AD
Neuroinflammation and AD
Neurotransmitter deficits
Neurotrophic factors
NF-B signaling and the pathogenesis of neurodegeneration
Nitric oxide and AD
Nogo receptor pathway
Oxidative stress and AD
Prostaglandins and AD
Quinolinic acid and AD
Retromer deficiency
Serotonin and AD
Spread of neurodegeneration
Synaptic failure in AD
Transmission of AD
Ubiquitin-proteasome system in pathogenesis of AD
Risk factors in the etiology of AD
Aging and developmental abnormalities of the cholinergic system
Cholesterol, dietary lipids, and Aβ
Epigenetic link between aging and AD
Exposure to magnetic fields
Family history of AD
Homocysteine and AD
Hypertension and AD
Level of education/type of job and risk of AD
Metals and AD
Proneness to psychological distress and risk of AD
Reduced muscle strength
Sleep deprivation
Traumatic brain injury and AD
Vascular risk factors for AD
Vitamin B12 and folate
AD versus non-dementing changes in the aging brain
AD and cognitive impairment with aging
Pathomechanism of memory impairment and AD
Concluding remarks on pathophysiology of AD
Genetics of AD
Familial AD
Molecular genetics of familial AD
Presenilins and calcium channel pathogenesis of familial AD
Presenilin-1 mutations and familial AD
Late onset AD
Genomics of AD
Introduction to genomics
Genes associated with Alzheimer disease
AlzGene database
ApoE genotype and nitric oxide
ApoE genotype modulates AD phenotype
APOE genotype and age-related myelin breakdown
ApoE receptor interaction with NMDA receptor
ApoE and ApoER2
ApoE receptor LR11 as regulator of A
Arctic mutation
BCHE gene
BRCA1 and AD
CALHM1 polymorphism and AD
Genetic variants associated with early-onset AD
Genetic variants associated with late-onset AD
ApoE polymorphisms associated with LOAD
BMI1 mutations
Copy number variation (CNV) in LOAD
CYP46 and risk for AD
DAPK1 gene variants and AD
LRRTM3 as a candidate gene for AD
MTHFD1L gene variant associated with AD
Mutation in APP gene with protective effect against AD
OGG1 mutations associated with AD
SORL1 gene in AD
TOMM40 gene and risk of AD
TREM2 variants in AD
International Genomics of Alzheimer's Project
Sequencing in Alzheimer disease
Whole genomic sequencing in AD
Single-cell RNA sequencing in AD
Molecular neuropathology
Gene recombination in AD
Role of microRNAs in AD
DNA methylation in AD
AD as a polygenic disorder
Proteomics of AD
Application of proteomic technologies to study AD
Disturbances of interaction of nervous system proteins
Protein misfolding in AD
Common denominators of AD and prion diseases
Metabolomics of AD
Glucose hypometabolism in AD

2. Diagnostic Procedures for Alzheimer Disease
Importance of the diagnosis of Alzheimer disease
Methods of diagnosis of AD
Self-administered olfactory test
Neuropsychological testing
Assessment and evaluation
7-minute screen
15-point risk index
Activities of Daily Living
Alzheimer Disease Cooperative Study
Artificial intelligence-based test for diagnosis of AD
CDR-SOB score
Clinician's Interview-Based Impression of Change
DETECT System
Measurement of aggregation in anterior segment of the eye
Resource Utilization in Dementia Battery
Quantitative EEG for investigation of early AD
EEG-based bispectral index
Event-related potentials
Correlation of electrical activity of the brain with cognition
Concluding remarks on the role of EEG in diagnosis of AD
Ocular findings for the diagnosis of AD
Early detection of cataract associated with AD
Retinal imaging to detect Aβ deposits
Laboratory methods for diagnosis of AD
Examination of cerebrospinal fluid
Monitoring of synthesis and clearance rates of Aβ in the CSF
Molecular diagnostics for AD
Genetic tests for AD
ApoE genotyping
Gene expression patterns in AD
Monoclonal antibody-based in vitro diagnosis of AD from brain tissues
Multi-tissue RNA signature of aging as diagnostic for AD
Biomarkers of AD
The ideal biomarker for AD
CSF biomarkers of AD
CSF sulfatide as a biomarker for AD
Glycerophosphocholine as CSF biomarker in AD
Protein biomarkers of AD in CSF
Tau proteins in CSF
Tests for the detection of Aβ in CSF
Tests combining CSF tau and Aβ
Lumipulse G CSF assays for routine diagnosis of AD
Concluding remarks about CSF biomarkers of AD
Urine tests for AD
Blood tests for AD
A serum protein-based algorithm for the detection of AD
α2-macroglobulin as a biomarker of preclinical and early AD
Blood Aβ level as biomarker of AD
Blood test for AD based on heme oxygenase-1
Blood test for AD based on RNA hybridization
GSK-3 elevation in white blood cells
Lipid biomarkers for preclinical detection of AD
Lymphocyte Proliferation Test
Metabolomic biomarker profiling
MGAT3 as biomarker for prognosis of AD
MicroRNA-based test for AD
Protein kinase C in red blood cells
Tests based on protein biomarkers in blood
Skin test for early detection of AD
Saliva-based tests for AD
Saliva Aβ42 level as a biomarker of AD
Smell identification test
Nanotechnology to measure Aβ-derived diffusible ligands
Simultaneous measurement of several biomarkers for AD
Nutritional biomarkers in plasma of AD patients
Plasma biomarkers of drug response in AD
Biomarkers of disease modifying therapies for AD
Concluding remarks about biomarkers for AD
Imaging in AD
Computed tomography
Magnetic resonance imaging
Arterial spin labeling with MRI
Magnetic resonance microscopy
Magnetic resonance spectroscopy
Single photon emission computed tomography and modifications
Positron emission tomography
In vivo imaging of Aβ deposits by PET
Pittsburgh compound B and PET
Future prospects of the PET imaging in AD
In vivo detection of Aβ plaques by MRI
Imaging agents for Aβ and neurofibrillary tangles
Hyperspectral Raman imaging of neuritic plaques in AD
Targeting of a chemokine receptor as biomarker for brain imaging
Radioiodinated clioquinol as a biomarker for Aβ
In vivo imaging of tau by PET
Imaging neuroinflammation in AD by PET
Preclinical diagnosis of AD
Correlation of imaging with CSF biomarkers for early detection of AD
Meta-analysis of literature on imaging in AD
Alzheimer Disease Neuroimaging Initiative
Computer aided diagnosis systems for AD based on imaging data
Concluding remarks on imaging for diagnosis of AD
Diagnosis of MCI and prediction of AD
Diagnosis of MCI
Computer-Administered Neurophychological screen for MCI
Infrared eye-tracking technology to detect MCI
MRI for detection of MCI
PET for detection of MCI
Role of APOE genotype in early MCI
Presymptomatic detection of AD
Biomarkers for AD screening
Biomarker changes in autosomal dominantly inherited AD
Blood test for preclinical diagnosis of AD
Gait analysis during cognitive tasks
Genetic screening for AD
PredictAD project
Prediction of AD in patients with MCI
Biochemical biomarkers in CSF for prediction of AD
Clinical and biochemical biomarkers for profiling prodromal AD
Combination of MMSE and a memory test for prediction of AD
Plasma protein biomarkers of conversion of MCI to AD
MRI for prediction of AD
Magnetoencephalography for detection of MCI and AD
MRI-based index to measure the severity of AD in MCI
Concluding remarks about prediction of AD in MCI
Criteria for diagnosis of AD
Role of biomarkers in diagnosis of AD dementia
Ethical aspects of diagnostics for AD
Genetic testing for AD
Ethical issues of brain imaging in AD
Monitoring of treatment of AD
Monitoring treatment of mixed AD and vascular dementia
Companies involved in diagnosis of AD

3. Management of Alzheimer Disease
Cholinergic approaches
Mechanism of action of cholinesterase inhibitors
Choline and lecithin
Duration of treatment with ChE inhibitors
Comparative studies of ChE inhibitors
Donepezil versus rivastigmine
Donepezil versus galantamine
Combination of cholinesterase inhibitors and a cholinergic precursor
An assessment and future prospects of anticholinergic therapies
Neuroprotection in Alzheimer's disease
Pharmacology of memantine
Clinical trials of memantine
Combination of memantine with ChE inhibitors
Monoamine oxidase inhibitors
Synaptoprotection in AD
Drugs for noncognitive symptoms in AD
ChE inhibitors for behavioral and psychological disorders in AD
Concluding remarks and other drugs for agitation in AD
Sensory stimulation
Non-pharmacological treatments of AD
Cerebrospinal fluid shunting
Deep brain stimulation
Exposure of the brain to electromagnetic fields for treatment of AD
Application of electrical fields for improvement of cerebral function
High-frequency electromagnetic field treatment of AD
Transcranial magnetic stimulation
Mental training for management of memory loss in AD
Microchip-based hippocampal prosthesis for AD
Omental transposition
Photo-induced inhibition of Aβ accumulation in AD
Scanning ultrasound for removal of Aβ
Vagal nerve stimulation
Nutritional therapies for AD
Cocktail of dietary supplements for AD
Docosahexaenoic acid
Ketogenic diet
Nicotinamide for the treatment of AD
Omega-3 fatty acids
Preventing decline of mental function with aging and dementia
Prevention of Alzheimer disease
Mental training
Physical exercise
Higher level of conscientiousness and decreased risk of AD
Nutritional factors in prevention of AD and MCI
Black and green teas
Caloric restriction
Cocoa flavonol consumption
Grapes and red wine
Vitamin D and docosahexaenoic acid
Drugs to prevent Alzheimer disease
Preimplantation genetic diagnosis of inherited Alzheimer disease
Presymptomatic detection of AD
Management of mild cognitive impairment
Slowing the progression of MCI to AD
Management of Down syndrome
Guidelines for use of anti-dementia drugs in clinical practice
Donepezil and/or memantine
General care of the Alzheimer disease patients
Strategies for the management of Alzheimer disease

4. Research in Alzheimer Disease
Animal models of Alzheimer disease
Lesional models
Cerebroventricular injection of Aβ in rats
Lentiviral vector-based models of amyloid pathology
AAV-mediated gene transfer to increase hippocampal A
Transgenic mouse models
Quantitative assessment of amyloid load in transgenic models
In vivo magnetic resonance microimaging in transgenic models of AD
Transgenic model of AD with suppression of Aβ production
Transgenic AD11 anti-NGF mice
Genetically altered mice with deficiency of vesicular ACh transporter
Limitations of mouse models of Alzheimer disease
Improved mouse models of AD expressing human genes
Cholesterol-fed rabbits as models for AD
Canine dementia as model for AD
Zebrafish model for AD
Transgenic invertebrate models of Alzheimer disease
Drosophila model of AD
Caenorhabditis elegans Alzheimer disease model
Correlation of studies in animal models and human clinical trials
Cell systems for AD research
In vitro neuronal cell Lines
Single-gene expression system for use in cell culture
Stem cells for testing efficacy of AD drugs
Transgenic cells
In silico models
Estimation of progression rates of Alzheimer disease
Clinical trial methods in Alzheimer disease
Molecular imaging as a guide to drug development
Use of MRI and PET in clinical trials
Cognitive-function assessment in clinical trials
Clinical trials in mild cognitive impairment
Research in AD as a basis for future therapies
Use of microarrays for studying pathogenesis of AD
Computational brain mapping in AD
Study of neurogenesis in AD
Study of 3D structure of Aβ
Solid-state NMR to study precursors of Aβ
Research in Alzheimer disease at academic centers
Role of NIH in AD research
NIH Clinical Trials Database for AD
Alzheimer Research Consortium
The National Institute on Aging and AD research

5. Drug Discovery & Development for Alzheimer Disease
Categories of drugs in development for AD
Memory-enhancing drugs
Enhancing memory by drugs that block eIF2α phosphorylation
Drugs based on cholinergic approaches
Butyrylcholinesterase inhibitors
Donepezil-tacrine hybrids
Drugs modulating gamma-aminobutyric acid receptors
Methanesulfonyl fluoride
Muscarinic receptor modulators
Muscarinic M1 agonists
Muscarinic M2 antagonists
Nicotine and nicotinic receptor modulators
Nicotinic receptor modulators
Somatostatin release enhancers
Glutamate receptor modulators
Physiology and pharmacology of glutamate receptors
NMDA receptor ion channel complex
Metabotropic glutamate receptors
Glutamate receptor modulators as potential therapeutics for AD
AMPA modulators
Glutamate release inhibitors
Drugs affecting multiple neurotransmitters
Vaccines for AD
Active immunization with Aβ
AN-1792 vaccine
DNA vaccine for AD
Strategies to avoid undesirable effect of Aβ vaccination
Passive immunization in AD
Passive immunization with MAbs
Clinical trials of MAbs in AD
Delivery of the passive antibody directly to the brain
Systemic injection of MAbs to treat AD
Combination of Aβ immunotherapy and CD40-CD40L blockade
Shaping the immune responses elicited against Aβ
Delivery of AD vaccines
Gene vaccination
Modified Aβ nasal vaccine
Transdermal Aβ vaccination
Other vaccines for AD
Nasal vaccination with Proteosome adjuvant
T cell vaccination with glatiramer acetate adjuvant
Early start of immunotherapy for clearing Aβ plaques
Reversal of cholinergic dysfunction by anti-Aβ antibody
Immune modulation via Toll-like receptors to reduce Aβ
Mechanisms by which Aβ antibodies reduce amyloid accumulation in the brain
Perspectives on vaccines for AD
Companies involved in AD vaccines
Inhibition of amyloid precursor protein aggregation
Secretase modulators
Neuroprotection by α-secretase cleaved APP
Inhibitors of β-secretase
Inhibitors of γ-secretase
Amyloid-derived diffusible ligands
GABA receptor modulation by etazolate and APP processing
Depletion of serum amyloid P
Drugs that inhibit the formation of Aβ
Cadmium telluride nanoparticles prevent Aβ fibril formation
Chelation therapy for AD
Clioquinol and PBT2
Copper chelation by FKBP52
Zinc chelation from amyloid plaques
Next generation multifunctional chelating agents for AD
Heparin and its derivatives
A reassessment of the role of heparin in AD
Heparan sulfate
Imatinib mesylate
Flurbiprofen analogs with Aβ42-lowering action
Nitric oxide-donating NSAIDs
In vivo demonstration of the effects of NSAIDs on brain in AD
Platinum-based inhibitors of Aβ
Retro-inverso peptide inhibitor
Selective serotonin reuptake inhibitor
Small molecule drug discovery for inhibiting Aβ aggregation
Trojan-horse approach to prevent build-up of Aβ aggregates
Ubiquitin C-terminal hydrolase L1
Drugs to prevent the formation of NFTs
Tau suppression
Anti-tau antibodies
Tau aggregation inhibitor rember™
Microtubule stabilizers
ApoE4 as a therapeutic target in AD
Strategies to prevent deposits and enhance clearance of Aβ
4,5-dianilinophthalimide for disruption of Aβ1-42 fibrils
ABCA1 overexpression to lower amyloid deposits
Beta-sheet breakers
Blocking ApoE/Aβ interaction to reduce Aβ plaques
CD33 inhibitors
Clearance of Aβ across the blood-brain barrier
Clusterin for clearance of Aβ
Enhanced PKCє activity promotes clearance of Aβ
Galantamine-induced Aβ clearance
Inhibitors of Aβ dehydrogenase
Intravenous immune globulin
Monoclonal antibodies for removal of Aβ
Nanotechnology for removal of Aβ deposits
Role of matrix metalloproteinases in clearance of Aβ
Serum amyloid P component depletion
Small molecule DAPH for clearance of amyloid
Tramiprosate prodrug ALZ-801
Companies developing Aβ-directed therapeutics for AD
Ergot derivatives
Neuroprotective effect drugs not primarily developed for AD
Antiepiletic drugs
Antiinflammatory and antimicrobial drugs
Antimicrobial drugs against C. pneumoniae
PPAR-gamma agonists
Antidiabetic drugs
Antihypertensive drugs
Angiotensin-converting enzyme inhibitors
Angiotensin receptor blockers
Antiretroviral drugs
Drugs acting on estrogen receptors
Granulocyte-macrophage colony-stimulating factor
Gingipain inhibitors
Inhibitors of neuroinflammation
Interferon beta-1a
Pregnenolone sulfate
MAO-B inhibitors
Ladostigil tartrate
Methylene blue
Valproic acid
Future prospects of neuroprotection in AD
Targeting Cdk5 pathway
Dehydroascorbic acid
Synthetic catalytic scavengers
Vitamin E as antioxidant
Vitamin B for lowering homocysteine
Folic acid
Nanobody-based drugs for AD
Nitric oxide-based therapeutics for AD
Nitric oxide mimetics
iNOS inhibitors for AD
Novel drugs for AD from natural resources
Berberine chloride
Centella asiatica
Ginko biloba
Nostocarboline derived from cyanobacteria
Securinega suffruticosa
Withania somnifera
Cholesterol and AD
ACAT inhibitors
Role of gene for cholesterol ester transfer protein
Cholesterol 24S-hydroxylase as a drug target for AD
Selectively increase of ApoA-I production
Neurotrophic factors
Brain derived neurotrophic factor
Insulin-like growth factor-1
Nerve growth factor
Neotrofin (AIT-082)
Limitations of the use of NTFs for AD
Role of serotonin modulators in AD
5-HT1A receptor antagonists
5-HT6 antagonists
5-HT4 receptor agonists
Restoration of factors deficient in the aging brain
Reversal of cognitive impairment in aging by activation of creb protein
Reversal of cognitive impairment in aging by GDF11 protein
Restoration of repressor element 1-silencing transcription factor
Cell therapy for AD
Choroid plexus epithelial cells for AD
Stem cell transplantation for AD
Autologous adipose tissue derived mesenchymal stem cells
Neural stem cells transplantation
Neuronal differentiation of implanted NSCs enhanced by drugs
NSCs improve cognition in AD via BDNF
Potential benefits of grafting NSCs in AD
Use of autologous stem cells for dementia
Gene therapy for AD
ApoE gene therapy
APPsα gene transfer for rescuing synaptic failure in AD
FGF2 gene transfer in AD
Gene therapy for restoring brain cholesterol metabolism
Humanin gene therapy
Neprilysin gene therapy
NGF gene therapy
Targeting plasminogen activator inhibitor type-1 gene
Antisense approaches to AD
Antisense PNA in AD
Antisense tau in AD
RNAi approaches to AD
Development of miRNAs for AD therapy
Combined therapeutic approaches to AD
Drug delivery for Alzheimer disease
Delivery of biologicals across the BBB
Delivery of thyrotropin-releasing hormone analogs by molecular packaging
Nanoparticle-based drug delivery for Alzheimer’s disease
Transdermal drug delivery in Alzheimer's disease
Transdermal rivastigmine
Intranasal delivery of therapeutics for AD
Intranasal delivery of tacrine
Intranasal delivery of nerve growth factor to the brain
Circadian rhythms and timing of cholinesterase inhibitor therapy
Clinical trials for AD
Ongoing clinical trials of AD
Concluding remarks on clinical trials of AD
Drug discovery for AD
Drugs acting on signaling pathways
Activation of GTPase signaling by Cytotoxic Necrotizing Factor 1
Drugs to reverse inhibition of the PKA/CREB pathway in AD
Inhibition of the CD40 signaling pathway
JNK pathway as a target
Mitogen-activated protein kinase pathway as target
Protein kinase C activators
Electrophysiological detection of drug target for neuroprotection in early AD
Genomics-based drug discovery
High through screening for AD drug candidates
New chemical entities for AD by combining galantamine and memantine
Novel rivastigmine-hydroxycinnamic acid hybrids for AD
Novels targets/receptors for AD drug discovery
Activation of cerebral Rho GTPases
Activators of insulin-degrading enzyme
Blockade of TGF--Smad2/3 signaling in peripheral macrophages
Calcium channel blockers
Calcineurin inhibitors
Calpain inhibitors
Casein kinase 1
Drugs against arginine deprivation and immune suppression in AD
Heat shock protein 90 inhibitors
Histone deacetylase inhibitors
Inhibition of PDK1 to slow progression of both AD and prion disease
Neurotrophic compound J147
NF-B inhibitors
Kinases and phosphatases as targets for AD therapeutics
Neutral sphingomyelinase inhibitors
Phosphodiesterase inhibitors
Pin 1 as a target in AD
Protein phosphatase 5 as a neuroprotective in AD
Single drugs for multiple targets in AD
Src homology-containing protein-1 inhibitors
Targeting GABAergic system
TSPO ligands
Type 5 cyclic nucleotide phosphodiesterase inhibitors
Proteomics and drug discovery for AD
Small molecule compounds binding to neurotrophin receptor p75NTR
Targeting Vav in tyrosine kinase signaling pathway
LM11A-31 as p75NTR ligand
Pharmacogenomics of Alzheimer disease
Biomarkers and companion diagnostics for AD
Genotyping and AD therapeutics
Incor777poration of genetic diversity into mouse models of AD
Personalized therapy of AD
Regulatory aspects of drug development for AD
EMEA guidelines for drug development for AD
FDA guidelines for drug development for AD
Concluding remarks and future of AD research
Future for AD therapeutics

6. Markets & Finances of AD Care
Pharmacoeconomics of treatment of AD
Quality of Life in relation to economics of AD
Costs associated with Alzheimer disease
Pharmacoeconomics of donepezil
Pharmacoeconomics studies using rivastigmine
Pharmacoenonomics studies using galantamine
Pharmacoenonomics studies using memantine
Epidemiology of AD
Patterns of AD care in major markets
Care of AD patients in the US
Cost of care
Medicare and AD
Patterns of practice in AD care
Opinions of physicians’ organizations on drugs for dementia
Care of AD patients in the UK
Cost of care
Patterns of practice in AD care
NICE recommendations to NHS
Care of AD patients in Germany
Care of AD patients in France
Care of AD patients in Italy
Care of AD patients in Spain
Care of AD patients in Japan
Markets for AD diagnostics
Markets for AD therapeutics
Geographical markets for AD
Markets for currently approved drugs for AD
Markets for generic AD drugs
Future growth of AD market
Limitations of AD drug development by the biotechnology industry
Unmet needs in the management of AD
Drivers of AD markets
Increase of the aged populations
Increase in the number of approved drugs for AD
Limitations of the current therapies
Improvements in diagnosis
Increasing awareness of the disease

7. Companies
Profiles of companies

8. References

Table 1-1: Historical landmarks relevant to Alzheimer disease
Table 1-2: Clinical features of Alzheimer disease
Table 1-3: Non-Alzheimer dementias
Table 1-4: A guide to evaluation for MCI due to AD
Table 1-5: NINCDS-ADRDA Criteria for diagnosis of Alzheimer disease
Table 1-6: 2011 Revised criteria for diagnosis of dementia due to Alzheimer Disease
Table 1-7: Relation of mutations in amyloid precursor protein to CNS disorders
Table 1-8: Risk factors for Alzheimer's disease
Table 1-9: Genes linked to AD
Table 1-10: Abnormalities of expression of brain proteins in Down's syndrome and AD
Table 2-1: Classification of methods of diagnosis of Alzheimer disease
Table 2-2: Neuropsychological test batteries and scales for Alzheimer's disease
Table 2-3: Available molecular diagnostic tests for Alzheimer disease
Table 2-4: Biomarkers of AD in blood and CSF
Table 2-5: Characteristics of an ideal biomarker for Alzheimer disease
Table 2-6: Role of biomarkers in diagnosis of AD dementia
Table 2-7: Potential applications of fluid biomarkers of Alzheimer disease
Table 2-8: Companies involved in the diagnosis/monitoring of Alzheimer disease
Table 3-1: Classification of treatments for Alzheimer disease
Table 3-2: Cholinergic approaches used in the treatment of Alzheimer disease
Table 3-3: Categories of neuroprotective agents for Alzheimer disease
Table 3-4: Strategies for prevention of Alzheimer disease
Table 3-5: Guidelines for the treatment of dementia
Table 4-1: Transgenic mouse models of Alzheimer disease
Table 4-2: Correlation of studies in animal models with human clinical trials
Table 5-1: Classification of therapies in development for Alzheimer disease
Table 5-2: Drugs for AD targeting nACh receptors
Table 5-3: Ionotropic glutamate receptors
Table 5-4: Classification of mGluRs
Table 5-5: Glutamate receptor modulators as potential therapeutic agents in AD
Table 5-6: Companies involved in developing vaccines for AD
Table 5-7: Preclinical studies of secretase modulators
Table 5-8: Secretase modulators in clinical trials
Table 5-9: Companies developing Aβ-directed therapeutics for AD
Table 5-10: Innovative neuroprotective approaches for Alzheimer disease
Table 5-11: Herbal therapies for AD
Table 5-12: Novel drug delivery methods for Alzheimer disease therapies
Table 5-13: Clinical trials in Alzheimer disease
Table 5-14: Discontinued, failed or inconclusive clinical trials of Alzheimer disease
Table 6-1: Prevalence of AD in major markets 2019-2029
Table 6-2: Direct and indirect costs associated with Alzheimer disease
Table 6-3: AD market values from 2019-2029 in major world markets
Table 6-4: Markets for currently approved AD drugs 2019-2029
Table 6-5: Potential markets for drugs in development 2019-2029
Table 6-6: Limitations of AD drug development by the biotechnology industry
Table 6-7: Factors that drive AD markets
Table 7-1: Major players in Alzheimer's disease therapeutics
Table 7-2: Collaborations relevant to Alzheimer disease

Figure 1-1: Percentages of world population of people over the age of 65 according to more developed and less developed portions − 2000 to 2050.
Figure 1-2: Correlation between aging and AD in the US from 2000 to 2020
Figure 1-3: Prevalence of different types of dementia
Figure 1-4: Structure of tau in a brain with AD
Figure 1-5: Aβ deposits in the brain
Figure 1-6: Major pathological features of AD
Figure 1-7: Mechanisms of Aβ clearance
Figure 1-8: Pathways for Aβ-induced nerve cell death
Figure 1-9: Insulin signaling in Alzheimer disease and diabetes
Figure 1-10: Nitric oxide neurotoxicity and neuroprotection in relation to Alzheimer disease
Figure 1-11: Oxidative stress and Alzheimer disease
Figure 1-12: Role of proteosome inhibition in Aβ generation and neurodegeneration
Figure 1-13: Cholesterol-related pathways to AD
Figure 1-14: Pathomechanism of AD
Figure 2-1: Pathophysiology of biomarkers of AD in relation to the neuron
Figure 3-1: Metabolism of acetylcholine
Figure 3-2: Neuroprotective effective of galantamine in AD
Figure 3-3: Strategies for the management of Alzheimer disease
Figure 5-1: Therapeutic strategies based on amyloid hypothesis of AD
Figure 5-2: Activation of α7 nicotinic acetylcholine receptors
Figure 5-3: NMDA receptor ion channel complex.
Figure 5-4: Neurotoxicity due to misfolding of A1-42
Figure 5-5: Interactions of players in clinical trials of Alzheimer disease in the USA
Figure 5-6: Role of proteomics in drug discovery/development for Alzheimer disease
Figure 5-7: FDA industry interaction during drug development for AD
Figure 5-8: FDA’s accelerated approval pathway in early Alzheimer disease
Figure 6-1: Unmet needs in the management of Alzheimer disease

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