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Alzheimer Disease - New Drugs, Markets and Companies
Jain PharmaBiotech, Nov 2009, Pages: 505
Executive Summary
1. Clinical Features, Epidemiology and Pathology
Introduction
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
Mild cognitive impairment
Diagnostic criteria of AD
Epidemiology
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
Sp proteins as markers of neuronal death in AD
Role of tau in the pathogenesis of AD
Amyloid precursor protein
Relation of APP mutations to CNS disorders
Relation of APP to Aß deposits and pathogenesis of AD
APP intracellular domain
Role of secretases in amyloid cascade
Role of exosomal proteins
Role of nicastrin
Neurotixicity of Ab deposits
Relation of Aß deposits to synaptic activity
Dysfunction of TGF-ß signaling accelerates Aß deposition
Role of TMP21 in presenilin complexes and Ab formation
Role of Ab dimers in the pathogenesis of AD
Structure–neurotoxicity relationships of Aß oligomers
Ab deposit and clearance
Impairment of mitochondrial energy metabolism
Ab-binding alcohol dehydrogenase links AD to mitochondrial toxicity
Neural thread protein
Loss of synaptic proteins
AD and Down syndrome
Overlapping pathologies of AD and Parkinson disease
AD and age-related macular degeneration
Myelin hypothesis of AD
Blood-brain barrier in AD
Blood vessel damage in AD
Loss of serotonin 1A receptors in the brain
Factors in pathogenesis of AD
Astrocytes and AD
Axonal transport failure in AD
Cell-cycle hypothesis
Creatine and AD
Disturbances of interaction of nervous system proteins
DENN/MADD expression and enhanced pro-apoptotic signaling in AD
Gonadotrophins and AD
Glutamate transport dysfunction in AD
Innate immune system and AD
Insulin, diabetes and AD
Mechanisms underlying cognitive deficits in AD
Monoamine oxidase and AD
Neuroinflammation and AD
Neurotransmitter deficits
Neurotrophic factors
NF-kB 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
Spherotoxin
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 Ab
Exposure to magnetic fields
Family history of AD
Homocysteine and AD
Level of education/type of job and risk of AD
Metals and AD
Obesity
Proneness to psychological distress and risk of AD
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
Presenilins and calcium channel leak in pathogenesis of familial AD
Late onset AD
Genomics of AD
Introduction to genomics
Genes associated with Alzheimer disease
AlzGene database
ApoE gene
ApoE genotype and nitric oxide
APOE genotype and age-related myelin breakdown
ApoE receptor interaction with NMDA receptor
ApoE and ApoER2
ApoE receptor LR11 as regulator of Ab
Arctic mutation
CALHM1 polymorphism and AD
CLU, CRI and PICALM
CYP46 and risk for AD
DAPK1 gene variants and AD
Genetic variants associated with late-onset AD
LRRTM3 as a candidate gene for AD
OGG1 mutations associated with AD
SORL1 gene in AD
TOMM40 gene and risk of AD
Molecular neuropathology
AD as a polygenic disorder
Proteomics of AD
Introduction
Application of proteomic technologies to study AD
Protein misfolding in AD
Common denominators of AD and prion diseases
Amyloid fibrils as a common feature of AD and prion diseases
FE65 proteins and 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
Measurement of aggregation in anterior segment of the eye
Activities of Daily Living
Alzheimer Disease Cooperative Study
CDR-SOB score
Clinician's Interview-Based Impression of Change
Resource Utilization in Dementia Battery
DETECTä System
Electrophysiology
EEG-based bispectral index
Event-related potentials
Early detection of cataract associated with AD
Laboratory methods for diagnosis of AD
Monitoring of synthesis and clearance rates of Ab in the CSF
Molecular diagnostics for AD
Genetic tests for AD
ApoE genotyping
Gene expression patterns in AD
Molecular fingerprinting of the immune system in AD
Microarray-based tests for AD
Monoclonal antibody-based in vitro diagnosis of AD from brain tissues
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
Amyloid precursor protein
Tau proteins in CSF
Tests for the detection of Ab in CSF
Tests combining CSF tau and Ab
Urine tests for AD
Blood tests for AD
Blood Ab levels
Blood test for AD based on heme oxygenase-1
Blood test for AD based on RNA hybridization
GSK-3 elevation in white blood cells
Lymphocyte Proliferation Test
Protein kinase C in red blood cells
Tests based on protein biomarkers in blood
A skin test for early detection of AD
Nanotechnology to measure Ab-derived diffusible ligands
Simultaneous measurement of several biomarkers for AD
Plasma biomarkers of drug response in 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 Ab deposits by PET
In vivo detection of Ab plaques by MRI
Imaging agents for Ab and neurofibrillary tangles
Targeting of a chemokine receptor as biomarker for brain imaging
Radioiodinated clioquinol as a biomarker for Aß
Imaging neuroinflammation in AD
Preclinical diagnosis of AD
Meta-analysis of literature on imaging in AD
Alzheimer Disease Neuroimaging Initiative
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
PET for detection of MCI
MRI for detection of MCI
Presymptomatic detection of AD
PredictAD project
Use of biomarkers to predict AD in patients with MCI
Biochemical biomarkers in CSF for prediction of AD
Structural MRI biomarkers for prediction of AD
Magnetoencephalography for detection of MCI and AD
Concluding remarks about prediction of AD in MCI
Ethical aspects of diagnostics for AD
Genetic testing for AD
Ethical issues of brain imaging in AD
Companies involved in diagnosis of AD
3. Management of Alzheimer Disease
Introduction
Cholinergic approaches
Mechanism of action of cholinesterase inhibitors
Choline and lecithin
Donepezil
Rivastigmine
Galantamine
Duration of treatment with ChE inhibitors
Comparative studies of ChE inhibitors
Donepezil versus rivastigmine
Donepezil versus galantamine
An assessment and future prospects of anticholinergic therapies
Neuroprotection in Alzheimer's disease
Memantine
Combination of memantine with ChE inhibitors
Monoamine oxidase inhibitors
Selegiline
Synaptoprotection in AD
Drugs for noncognitive symptoms in AD
Antidepressants
Antipsychotics
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
Management of memory loss in AD
Application of electrical fields for improvement of cerebral function in AD
Vagal nerve stimulation
Cerebrospinal fluid shunting
Omental transposition
Microchip-based hippocampal prosthesis for AD
Nutritional therapies for AD
Cocktail of dietary supplements for AD
Docosahexaenoic acid
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
Caloric restriction
Nutritional factors in prevention of AD
Grapes and red wine
Black and green teas
Caffeine
Drugs to prevent Alzheimer disease
Preimplantation genetic diagnosis of inherited Alzheimer disease
Presymptomatic detection of AD
Management of mild cognitive impairment
Management of Down syndrome
Guidelines for use of anti-dementia drugs in clinical practice
General care of the Alzheimer disease patients
Strategies for the management of Alzheimer disease
4. Research in Alzheimer Disease
Introduction
Animal models of Alzheimer disease
Lesional models
Cerebroventricular injection of Ab in rats
Lentiviral vector-based models of amyloid pathology
AAV-mediated gene transfer to increase hippocampal Ab
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 Aß production
Transgenic AD11 anti-NGF mice
Genetically altered mice with deficiency of vesicular ACh transporter
Limitations of mouse models of Alzheimer disease
Cholesterol-fed rabbits as models for AD
Zebrafish model for AD
Transgenic invertebrate models of Alzheimer disease
Drosophila model of AD
Caenorhabditis elegans Alzheimer disease model
Cell systems for AD research
In vitro neuronal cell Lines
Single-gene expression system for use in cell culture
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 Ab
Solid-state NMR to study precursors of Ab
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
Introduction
Categories of drugs in development for AD
Memory-enhancing drugs
Enhancing memory by drugs that block eIF2a phosphorylation
Drugs based on cholinergic approaches
AP2238
Butyrylcholinesterase inhibitors
Donepezil-tacrine hybrids
Drugs modulating gamma-aminobutyric acid receptors
Ganstigmina
Methanesulfonyl fluoride
Muscarinic receptor modulators
Muscarinic M1 agonists
Muscarinic M2 antagonists
Nicotine and nicotinic receptor modulators
Nicotine
Nicotinic receptor modulators
GTS21
Ispronicline
JWB1-84-1
Neuropeptide/neurotransmitters
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
Non-competitive NMDA modulators
AMPA modulators
Drugs affecting multiple neurotransmitters
Ensaculin
NS2330
RS-1259
Lecozotan
Vaccines for AD
Active immunization with Ab
AN-1792 vaccine
Complications in clinical trials with AN-1792
Effects of Ab vaccine on the brain
Strategies to avoid undesirable effect of Ab vaccination
Passive immunization in AD with monoclonal antibodies
Delivery of the passive antibody directly to the brain
Systemic injection of MAbs to treat AD
Combination of Ab immunotherapy and CD40-CD40L blockade
Shaping the immune responses elicited against Ab
Gene vaccination
Modified Ab nasal vaccine
Transdermal Ab vaccination
Other vaccines for AD
Nasal vaccination with ProteosomeÔ adjuvant
T-cell vaccination with glatiramer acetate adjuvant
Early start of immunotherapy to clear Ab plaques
Reversal of cholinergic dysfunction by anti-Ab antibody
Immune modulation via TRL9 to reduce Ab
Mechanisms by which Ab antibodies reduce amyloid accumulation in the brain
Perspectives on vaccines for AD
Companies involved in AD vaccines
Inhibition of amyloid precursor protein aggregation
Secretase inhibitors
Neuroprotection by a-secretase cleaved APP
b-secretase inhibitors
g-secretase inhibitors
Substrate-targeting by ?-secretase modulators
Amyloid-derived diffusible ligands
GABA receptor modulation by etazolate and APP processing
Depletion of serum amyloid P
Trojan-horse approach to prevent build-up of Ab aggregates
Drugs that inhibit the formation of Ab
22R-hydroxycholesterol
Acylaminopyrazole
Antihypertensive drugs
Valsartan
Chelation therapy for AD
Clioquinol and PBT2
Copper chelation by FKBP52
Zinc chelation from amyloid plaques
Next generation multifunctional chelating agents for AD
Tetrahydrocannabinol
NSAIDs
Flurbiprofen analogs with Ab42-lowering action
Nitric oxide-donating NSAIDs
In vivo demonstration of the effects of NSAIDs on brain in AD
Imatinib mesylate
Laminin
Paclitaxel
Phenserine
Tolserine
Platinum-based inhibitors of Ab
Heparin and its derivatives
A reassessment of the role of heparin in AD
Enoxaparin
Heparan sulfate
Scyllo-cyclohexanehexol
Ubiquitin C-terminal hydrolase L1
Drugs to prevent the formation of NFTs
Tau suppression
ApoE4 as a therapeutic target in AD
Strategies to enhance clearance of Ab
Removal of Ab deposits by nanotechnology
Enhanced PKC? activity promotes clearance of Ab
Role of matrix metalloproteinases in clearance of Ab
Small molecule DAPH for clearance of amyloid
Clearance of Aß across the blood-brain barrier
Therapeutics to reverse cerebral Ab deposits
4,5-dianilinophthalimide for disruption of Ab1-42 fibrils
ABCA1 overexpression to lower amyloid deposits
b-sheet breakers
Blocking ApoE/Ab interaction to reduce Ab plaques
Inhibitors of Ab dehydrogenase
Intravenous immune globulin
Meptides
SAN-61 for cleavage of fibril and soluble amyloid
Serum amyloid P component depletion
Companies developing Ab-directed therapeutics for AD
Antiinflammatory and antimicrobial drugs
Dapsone
Antimicrobial drugs against C. pneumoniae
PPAR-gamma agonists
Inhibitors of neuroinflammation
Cyclophosphamide
Etanercept
MW01-5-188WH
VP015
Antidiabetic drugs
Rosiglitazone
Pioglitazone
Nootropics
Acetyl-L-carnitine
Cerebrolysin
Ergot derivatives
Lisuride
Dihydroergocryptine
Neuroprotective effect drugs not primarily developed for AD
Angiotensin-converting enzyme inhibitors
Dimebolin
Drugs acting on estrogen receptors
Estrogen
Raloxifene
Neurosteroids
Pregnenolone sulfate
Dehydroepiandrosterone
Lithium
MAO-B inhibitors
Ladostigil tartrate
Memoquin
Methylene blue
Nimodipine
Testosterone
Valproic acid
Future prospects of neuroprotection in AD
Targeting Cdk5 pathway
Antioxidants
Colostrinin
Curcumin
Melatonin
Synthetic catalytic scavengers
Dehydroascorbic acid
Omega-3 fatty acids
Vitamins
Vitamin E as antioxidant
Vitamins to lower homocysteine
Folic acid
Aminopyridazines
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
Gilatide (from saliva of the Gila monster)
Huperzine-A
Hyperforin
Melissa officinalis
Nostocarboline derived from cyanobacteria
PTI-00703
Salvia
Securinega suffruticosa
Withania somnifera
ZT-1
Cholesterol and AD
Role of statins in reducing the risk of Alzheimer disease
Neuroprotective effect of statins unrelated to cholesterol lowering
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
Activity-dependent neuroprotective protein
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
Xaliproden
5-HT1A receptor antagonists
5-HT6 antagonists
5-HT4 receptor agonists
PRX-03140
Cell therapy for AD
Stem cell transplantation for AD
Potential benefits of grafting NSCs in AD
NSCs improve cognition in AD via BDNF
Drugs for enhancing neuronal differentiation of implanted NSCs
Implantation of encapsulated cells for delivering NGF
Gene therapy for AD
ApoE gene therapy
Humanin gene therapy
Neprilysin gene therapy
NGF gene therapy
Targeting plasminogen activator inhibitor type-1 gene
Antisense approaches to AD
RNAi approaches to AD
Combined therapeutic approaches to AD
Drug delivery for Alzheimer disease
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
Drugs for AD that were discontinued in clinical trials
Evaluation of clinical trials of AD
Monitoring of cognitive function during clinical trials
Drug discovery for AD
Genomics-based drug discovery
Proteomics and drug discovery for AD
High through screening for AD drug candidates
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
Small molecule compounds binding to neurotrophin receptor p75NTR
Targeting Vav in tyrosine kinase signaling pathway
Novels targets/receptors for AD drug discovery
Activation of cerebral Rho GTPases
Blockade of TGF-b-Smad2/3 signaling in peripheral macrophages
Blockers of Aß calcium channel
Casein kinase 1
Cyclin-dependent kinase-5
Heat shock protein 90 inhibitors
Histone deacetylase 1
Inactivation of aph-1 and pen-2 reduces APP cleavage
NF-kB inhibitors
Kinases and phosphatases as targets for AD therapeutics
Phosphodiesterase inhibitors
Pin 1 as a target in AD
Protein phosphatase 5 as a neuroprotective in AD
Src homology-containing protein-1 inhibitors
Targeting GABAergic system
Pharmacogenomics of Alzheimer disease
Personalized therapy of AD
Genotyping and AD therapeutics
Biomarkers of AD/companion diagnostics for cholinesterase inhibitors
Regulatory aspects of drug development for AD
EMEA guidelines for drug development for AD
Concluding remarks and future prospects of drugs for AD
6. Markets & Finances of AD Care
Introduction
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
A comparison of pharmacoenonomics outcomes with different ChE inhibitors
Pharmacoenonomics studies using memantine
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
Retraction of 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
Statins
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
Introduction
Profiles of companies
Collaborations
8. References
Tables
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: NINCDS-ADRDA Criteria for diagnosis of Alzheimer disease
Table 1-5: Relation of mutations in amyloid precursor protein to CNS disorders
Table 1-6: Risk factors for Alzheimer's disease
Table 1-7: Genes linked to AD
Table 1-8: 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: Classification of biomarkers of AD in blood and CSF
Table 2-5: Characteristics of an ideal biomarker for Alzheimer disease
Table 2-6: Companies involved in the diagnosis 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 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: Companies developing Ab-directed therapeutics for AD
Table 5-8: Innovative neuroprotective approaches for Alzheimer disease
Table 5-9: Herbal therapies for AD
Table 5-10: Novel drug delivery methods for Alzheimer disease therapies
Table 5-11: Clinical trials in Alzheimer disease
Table 5-12: Discontinued, failed or inconclusive clinical trials of Alzheimer disease
Table 6-1: Direct and indirect costs associated with Alzheimer disease
Table 6-2: Prevalence of AD in major markets 2008-2018
Table 6-3: AD market values from 2008-2018 in the seven major world markets
Table 6-4: Markets for currently approved AD drugs 2008-2018
Table 6-5: Potential markets for drugs in development 2008-2018
Table 6-6: Limitations of AD drug discovery and 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
Figures
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: Prevalence of different types of dementia
Figure 1-3: Mechanisms of Aß clearance
Figure 1-4: Nitric oxide neurotoxicity and neuroprotection in relation to Alzheimer disease
Figure 1-5: Oxidative stress and Alzheimer disease
Figure 1-6: Role of proteosome inhibition in Aß generation and neurodegeneration
Figure 1-7: Pathomechanism of AD
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: NMDA receptor ion channel complex
Figure 5-2: Neurotoxicity due to misfolding of Ab1-42
Figure 5-3: Role of proteomics in drug discovery and development for Alzheimer disease
Figure 6-1: Unmet needs in the management of Alzheimer disease
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