Alzheimer's disease

ALZHEIMER’S DISEASE
DR. RESU NEHA REDDY
FINAL YEAR PG

CASE STUDY
A 75-year-old man was brought with a h/o progressive
functional decline, so much so that he now needs to be
looked-after all the time. He misplaces his daily need
articles, forgets what he said few minutes ago, is unable
to perform simple calculations, mixes up what
happened today and what happened yesterday, has
poor control of emotions, but vision, hearing and other
sensations are well preserved, and there is no gross
ataxia.

OBJECTIVES
 Introduction
 History
 Risk factors
 Pathophysiology
 Symptoms
 Diagnosis
 Non pharmacological treatment
 Drugs used in treatment of Alzheimer`s
 Recent advances
 Screening methods
 Summary
 References

INTRODUCTION
 Alzheimer's disease (AD) is a progressive, neurodegenerative disorder in elderly (≥ 60
years)
 Characterized by
 Memory loss (92%)
 Confusion (71%)
 Short attention span (63%)
 Declining sense of direction (53%)
 Personality changes (31%)
 ≈1 in 8 > 65 years

46.8 million
Prevalence of Alzheimer`s Disease

Deaths per million persons in 2012

Prevalence of Alzheimer`s Disease
INDIA
> 4 million people (3rd Highest case load in the World)
China > U.S > India
India's dementia and Alzheimer's ≈ 7.5 million by the end of 2030

Alzheimer`s Disease
TOM FEARS BETTY ROBINSON BILL QUACKENBUSH RONALD REAGAN
β

HISTORY
Alzheimers disease was first described by German Physician Dr Alois
Alzheimer in 1906
Alois Alzheimer Auguste Deter

HISTORY
Alois Alzheimer
First reported
pathologically
documented
Emil Kraepelin
Named the disease
Schottyky J
The first reported
kindred with
pathologically
documented AD
1906 1910 1984
Glenner & Wong
Amyloid β protein
identified from
Plaques
1986
Goate et al.
Misense mutation in
APP gene identified
1932 1987 1991
Tau protein
Identified in
Neurofibrillary
Tangles
1992
Tacrine
First Alzheimer’s
Drug Trial
Amyloid
cascade hypothesis

HISTORY
PSEN1 E280A
Mutation
reported
PSEN1 E280A
Increases Aβ42
deposition
Clinical Features of
EOAD pE280A
Presenilin-1
mutation
1995 1996 1999
 Alzheimer’s vaccine
successful in mice
PSEN-1 is catalytic
unit of γ-Secretase
20001997 2002
Aβ25-35 induces
apoptosis via OS
mechanism
DNA Damage does
not correlate with
Aβ/ NFT in E280A
FAD

HISTORY
Proposed Clinical stages
 Asymptomatic MCI
 Symptomatic MCI
 MCI
 Dementia
Fibrillar Aβ begins
to accumulate in
carriers at a mean
age of 28 years
2011 2012 2014
Passive Aβ
immunization
started
API
Alzheimer’s
Prevention
Initiative Launched
MRI anomalies &
Aβ1-42
overproduction in
CSF & plasma
CA 1 neuronal loss
related with
epilepsy
2004

Histological Hallmarks of AD
SENILE PLAQUES NEUROFIBRILLARY TANGLES
SP  Neocortex, Hippocampus & in several Subcortical areas
NFT density correlates with disease duration and severity of dementia
SENILE PLAQUES

Gross appearance of brain of AD

Vulnerable Neurons in AD
• Basal forebrain cholinergic system (Nucleus basalis)
• Monoaminergic system
• Hippocampus (CA1 and CA2 pyramidal cells)
• Amygdala
• Entorhinal cortex
• Neocortex

Effects of neuronal death in AD
• Hippocampus & Enthorhinal cortex  Memory and learning
• Cortex & Basal forebrain cholinergic systems  Memory and attention
• Amygdala & other deep nuclei  Behavior and emotions

• Onset age: < 65 years
• ≈ 5%
• Genes: APP,PSEN1,PSEN2
Early onset
AD
• Onset age: > 60-65 y
• ≈ 90-95%
• Genes: APOE
Late Onset
AD
Categories of Alzheimer's Disease

Risk Factors for Alzheimer`s Disease
1) AGE
2) SEX
Females are more effected
< 65
65-75
> 85
75-84

3) HEREDITY
EARLY ONSET
 Alterations on chromosome 1, 14 and 21
 Mutation on chromosome 14  PRESENILIN 1 (PSEN1)
 Mutation on chromosome 1  PRESENILIN 2 (PSEN2)
 PSEN1 & 2 encode for membrane protein involved for APP
 Mutations  activity of γ-secretase  βAP formation
 APP is encoded on chromosome 21
 Mutation on APP gene  overproduction of βAP

3) HEREDITY
LATE ONSET
 Due to apo-lipoprotein E (apoE) gene
 Gene responsible for production of apoE gene – chromosome 19
 Inheritance of apoE4 allele posses genetic risk
Degree of risk depends on:
Number of copies of apoE4 genes
Age
Ethnicity

4) Race & Ethnicity
 African-Americans: 2 times greater risk
 Hispanics: 1.5 times greater risk
 Cardiovascular risk factors more common
 Lower levels of education, socioeconomic status

5) Other factors
• Smoking
• Obesity
• Head injury
• Low educational levels
• Environmental factors – Aluminum, Mercury & Viruses
• Vascular disease – Stroke
• Diabetes
• Hypertension
• Hypercholesterolemia
• Down’s syndrome

Pathogenesis of Alzheimer’s Disease
 βAP aggregation & deposition  plaque formation
 Hyperphosphorylation of Tau protein  NFT development
 Inflammatory processes
 Dysfunction of neurovasculature
 Oxidative stress
 Mitochondrial dysfunction

AMYLOID CASCADE HYPOTHESIS

NEUROFIBRILLARY HYPOTHESIS

 INFLAMMATORY MEDIATORS:
 Brain amyloid deposition is associated with local inflammatory and
immunologic alleviations.
 It is associated with release of Nitric oxide, cytokines, other radical species &
complement factors that injure neurons and promote inflammation.
 CHOLINERGIC HYPOTHESIS:
 Loss of cholinergic activity correlates with AD severity.
 In late AD, number of cholinergic neurons are decreased, loss of nicotinic
receptors in hippocampus and cortex.

 OTHER NEUROTRANSMITTER ABNORMALITIES:
 Glutamate & other excitatory amino acid NTs act as potential neurotoxins for AD
 If glutamate remains in synapse for a long period of timedestroys nerve cells
 Blocking of NMDA receptors decreases the glutamate activity in synapse –
decreases cellular injury in AD

 BRAIN VASCULAR DISEASE & HIGH CHOLESTROL:
 ApoE lipoprotein carries cholesterol in blood through brain.
 ApoE4 is associated with increased deposition of βAP.
 Increased cholesterol in brain neurons  alter membrane functioning  leads
to plaque formation  Alzheimer’s disease.

Symptoms of Alzheimer`s Disease

Stages of Alzheimer’s Disease
Stages Mild Moderate Severe
Symptoms • Recent memory loss
• Language problems
• Mood and
personality changes
• Diminished
Judgment
• Increased memory loss
• Behavioral &
personality changes
• Unable to learn or
recall new information
• Wandering, Agitation &
Aggression
• Confusion about time &
place
• Require assistance
with ADLs
• Loss of recognition of
familiar people or places
• Total loss of verbal skills
• Unstable gait
• Incontinence
• Motor disturbances
• Bedridden
• Dysphagia
• Poor / No ADLs
• LTC placement
ADL = Activities of Daily Living
LTC = Long-Term Care

Death due to Alzheimer’s disease
 Life expectancy  Reduced
 Following diagnosis  3 – 10 years
 < 3% of people live > 14 years
 Pneumonia & Dehydration  Death

Diagnosis of Alzheimer’s Disease
Cognitive testing:
Mini- Mental Status Examination
Cutoff = 24/30
SCORE DIAGNOSIS
27 – 30 Normal
21 – 26 Mild cognitive impairment
11 – 20 Moderate cognitive impairment
0 – 10 Severe

Diagnosis of Alzheimer’s Disease
Laboratory tests:
Circulatory miRNA
Inflammatory biomarkers
Brain imaging:
CT scan
MRI
SPECT
PiB PET – Florbetapir
CSF Examination

No medications or supplements  Decrease risk of AD
No treatments stop or reverse AD progression
Though, temporarily improve symptoms

Non Pharmacological Approaches

Non Pharmacological Approaches
Cognitive/ Emotion-oriented Interventions:
Reminiscence Therapy
Simulated Presence Therapy (SPT)
Validation Therapy
Reality Orientation Therapy
Sensory Stimulation Interventions:
Acupuncture
Aromatherapy
Light Therapy
Massage & Touch Therapy
Music Therapy
Snoezelen Multisensory Nerve Stimulation
Transcutaneous Electrical Nerve Stimulation (TENS)

Brain Training
 Crosswords
 Learning a new language
 Reading a book
 Undertaking further education
 Can intensive computerised training stop progress of cognitive decline and
onset of dementia?  Studies ongoing

Physical Activity
 Still no randomised trials available yet
 People who exercise  Slower loss of brain tissue
 People who exercise regularly are less likely to have vascular disease
which ↑’s risk of AD
 Reduce - stress, anxiety and depression
 3 types of exercise program – sustained aerobic exercise, weight training
and flexibility and balance training

Diet in AD
 A recent study looked at 3 different diets:
1. Mediterranean diet
2. DASH diet (Dietary Approaches to Stop Hypertension)
3. MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay)
 Natural plant-based foods, berries and green leafy vegetables, limited
saturated fats  Benefit brain health

TARGETS OF
DRUG ACTION
FOR AD
.
.
.
.

Drugs used in Alzheimer’s disease
Experimental Drugs
(Role under evaluation)
Approved Drugs
(Role well established)
Cholinesterase
Inhibitors
NMDA
Antagonists
• Donepezil
• Rivastigmine
• Galantamine
• Memantine
Nicotinic
Receptor
Agonists
• 4 OH-GTS-21
Antioxidants
• Ginkgo biloba
• Vitamin E
• Melatonin
PPAR γ Agonist
• Pioglitazone
Gamma
Secretase
Inhibitor
• Semagacestat
5HT-6
Antagonist
• SB-271046
Statins
• Simvastatin
• Pravastatin
Others
• Heavy metal chelators
• Estrogens
• Anti-inflammatory drugs

TACRINE
DONEPEZIL
RIVASTIGMINE
GALANTAMINE
•CHOLINESTERASE INHIBITORS

Cholinergic Hypothesis
 Role
– Ach is an important neurotransmitter in brain  Memory
 Impact
– Loss of ACh in AD  Impairment of memory
 Treatment approach
– Enhancement of cholinergic function may stabilize or improve cognitive
function  Behavior and daily functioning

Tacrine
• Aminoacridine
• Dose dependent effect: 40 mg-160 mg/day
• Half life : 3 - 5 hrs
• Metabolized by CYP450
• Adverse effects:
• Nausea, vomiting, diarrhoea
• Hepatotoxicity
• No longer actively marketed

Donepezil
• Long t ½ – 70 hrs
• Dose = 5 -10 mg daily
• Several controlled trials  modest benefits in cognition and behaviour
• Not hepatotoxic
• Adverse effects: Nausea, diarrhoea, vomiting, fatigue, muscle cramps, bradycardia
• Generally safe & well tolerated

Rivastigmine
• Inhibits both AChE & BChE
• Higher affinity for brain AChE than peripheral
• Half-life of 2 hours
• Dosing BD of 3 - 12 mg/day
• Patch 9.5 mg/24 hr available
• Metabolism independent of hepatic CYP450 system
• GI adverse events are common, including weight loss

Galantamine
• Galantamine has a dual mechanism of action
– Competitive inhibition of AChE
– Allosteric modulation of presynaptic and postsynaptic nicotinic receptors
• Galantamine improves major aspects of AD
(eg: cognition, behavior, function)
• Generally safe and well tolerated

Dual Mechanism of Action
Postsynaptic
nerve terminal
M receptor N receptor
Presynaptic nerve
terminal
Galantamine
 ACh and other
neurotransmitters
M receptor N receptor
ACh
• Choline
• Acetic acid
Galantamine
N = nicotinic
M = muscarinic
ACh = acetylcholine

AChE Inhibitors: Pharmacokinetic
Characteristics
AChE Inhibitors
Dual AChE/
BuChE Inhibitor
Characteristic Donepezil Galantamine Rivastigmine
Plasma half-life (hour)
Brain half-life
~70
70
~6
6
~1
12
Elimination
pathway Liver
50% kidney
50% liver Kidney
Metabolism by
2D6/3A4 isoenzymes Yes Yes Minimal

NMDA receptor antagonists
 Glutamate  Excitatory
neurotransmitter in brain
 Acts on post synaptic NMDA receptors
 Glutaminergic overstimulation may
result in neuronal damage
(excitotoxicity)
 Dementia and pathogenesis of
Alzheimer`s disease

Memantine
• NMDA receptor antagonist approved  Moderate to severe AD
• Uncompetitive
• Low affinity
• Voltage dependent
• Interacts with Mg2+ binding site of channel to prevent excessive
excitation while sparing normal functions

Memantine (Pharmacokinetics)
• 100 % bioavailability
• T ½ = 60-80 hrs
• Rapidly crosses BBB
• Little metabolism, 75% -90% excreted unchanged in urine
• Minimal drug interactions and food interaction
• Starting dose – 5 mg OD , recommended target dose is 20 mg/day

Memantine (Adverse effects)
• Dizziness
• Headache
• Confusion
• Constipation
• Agitation

EXPERIMENTAL DRUGS
(ROLE UNDER EVALUATION)

GAMMA SECRETASE INHIBITORS
 SEMAGACESTAT  Candidate drug
↓ Plasma and CSF A- Concentration
 IDENTITY -1 Trial Phase 3 started in March 2008
 Interrupting Alzheimer's Dementia By Evaluating Treatment Of Amyloid
Pathology

GAMMA SECRETASE INHIBITORS
 IDENTITY - 2 trial started in September 2008
 Did not slow disease progression
 Worsened cognition and the ability to perform ADL
 ↑ risk of skin cancer, rash and hair discolouration
 Eli Lily halted the development

ANTIOXIDANTS
 Recent research  Link between antioxidant intake and decreased
incidence of Alzheimers
Curcumin
Ginko biloba
Vitamins
Green tea

Curcumin (Turmeric)
 Anti-oxidant, anti-inflammatory & anti-aggregation
 It binds Aβ and reduces amyloid plaque burden in mice
 Preliminary results show reduced rate of cognitive decline in normal
healthy elderly receiving curcumin compared to placebo – only short
time frame (6 months) and small numbers – larger studies needed.
 Limited studies in AD patients have so far failed to show any benefit
clinically.

GINKO BILOBA
 Ancient use in China and Japan as a tonic
 Poor circulation
 Inner ear disorders
 Absent-mindedness
 Dementia
 Depression
 Hypertension in the elderly
 Impotence in men
 Chinese used leaves and nuts

GINGKO BILOBA
FLAVINOIDS TERPENOIDS
REDUCE FREE RADICALS
BILOBALIDESGINGKOLIDES
INHIBITS PLATELET
ACTIVATING FACTOR
(PAF)
REDUCE INFLAMMATION
PROTECTS NERVE
CELLS AND
REGENERATES MOTOR
NERVE CELLS

Physiologic Mode of Action Cont’d
 Acts by releasing NO & PGI2
 ↑ blood flow  ↑oxygen & nutrient delivery tissues  Brain
 ↓ blood viscosity
 ↑ in the release of neurotransmitters
 Antioxidant activity
 Prevention of free radical damage

Side effects
 Hemorrhage
 Hematoma
 Hyphema (bleeding in eye)
 In all trials < 0.5% reported minor
side effects including headaches, GI
distress and allergic skin reactions.

Vitamins
 Insufficient evidence  low levels of vit B12 in elderly ↑ risk for
dementia or that supplements improve performance
 Again, studies looking at folate supplementation have been inconsistent
 In 2014 a group of Oxford University researchers  involving 22,000
people and concluded that taking B vitamins and folate doesn’t slow
mental decline as we age, nor is it likely to prevent AD

Vitamins
 Vitamin D  Anti-oxidant and anti-inflammatory properties
 not clear  Vit D deficiency  Cognition
 Early laboratory evidence that Vitamin D receptor may help regulate
clearance of Aβ from the brain
 No firm scientific evidence yet that Vit D supplementation will have
positive effect on cognition

 Vitamins E, C & A – all powerful anti-oxidants
 Epidemiological studies  low intake ↑ dementia risk, but inconsistent
association
 Multiple clinical trials  Did not alter cognitive outcomes in MCI, AD or
healthy elderly but results still debated
Vitamins

Fish oil
 Omega-3 fatty acids found in fish oil and nuts – Neuroprotective
 Studies have failed to show any improvement in cognition
 In elderly without AD – inconclusive evidence
 Further large –scale studies needed

PPAR  agonists
 PPAR  agonists inhibit inflammatory
gene expression , alter Amyloid 
homeostasis & exhibit neuroprotective
effects
 15-30 mg Pioglitazone daily
 Improved agitation & regional cerebral
blood flow in parietal lobe
 Cognitive and functional
improvement
PPARγ activation
Modulate the microglial
response to amyloid
deposition
Increases Aβ phagocytosis
Decreases cytokine release
Neuroprotective effects

Statins
 Higher Cholesterol risk factor for AD
 Lovastatin prevented death of nerve cells in animal experiments
 Results of various studies not promising
 No difference between drug and control in terms of dementia,
cognitive function and neuropsychological tests

Estrogens
 AD more common in postmenopausal women
 Estrogen
 Modulate ApoE gene
 ↑ APP metabolism
 Protects against oxidative stress
 ↑Cerebral blood flow
 Prevent neuronal atrophy
 Clinical trials are inconclusive

NSAIDS
 Inhibit COX enzymes
 ↓Production of cytokines & microglial activation
 ↓ Platelet aggregation
 ↓ iNOS
 ↓ Beta secretase
 Large number of therapeutic trials of NSAID’s in AD (1993-2004)
 Ibuprofen, Indomethacin, Naproxen, Celecoxib , Rofecoxib & Prednisolone
 All were negative

Heavy metal chelators
 Amyloid beta plaques bind copper and zinc & removal of these metal
ions promotes dissolution of Plaques
 Levels of iron & zinc abnormally ↑ in brain in AD
 Desferrioxamine : ↓ dementia in a trial
 Clioquinal: Regression of Amyloid plaques in animal models of AD

Nicotinic receptor agonists
 α4β2 & 7 nAChR types localized in areas of brain
 Long term memory & Learning
7 nAChR agonist :
 4 OH-GTS21
 Protective action on cholinergic neurons
 Antiamnestic effect
 EVP-6124: Currently in phase2

5-HT6 receptor antagonists
 5HT6 receptor (functionally excitatory)  Co-localized with GABAergic
neurons  overall inhibition of brain activity
 In parallel with this, 5HT6 antagonists are hypothesized to improve
cognition, learning, and memory
 Latrepirdine, Idalopirdine & Intepirdine  Novel treatments for AD
 Phase III trials have failed to demonstrate efficacy
 Reduce appetite & produce weight loss

NOOTROPICS
Piracetam
Aniracetam
Blocks Ca channels
Inhibit AChE
Antioxidants
Synaptic &
mitochondrial
responsiveness
Improved Learning & Memory
Burdens of Aβ
Synaptic dysfunction
Inflammation
Apoptosis
Oxidative stress
Neuroprotective Potential
Anti-Alzheimer’s activity

Immunization For Alzheimers Disease?
 Transgenic animals were immunized with A42
 Either before the onset of AD-type neuropathologies (at 6 weeks of
age) or at an older age (11 months)
 When amyloid- déposition and several of the subsequent
neuropathological changes were well established

Immunization for Alzheimers disease?
 Immunization of the Young animals essentially prevented the
development of  -amyloid plaque formation, neuritic dystrophy and
astrogliosis.
 Treatment of the older animals also markedly reduced the extent and
progression of these AD-like neuropathologies.
 Hence the possibilty that immunization with amyloid-b may be effective
in preventing and treating AD

Anti-Amyloid strategies - Immunotherapy

Anti-Amyloid strategies - Immunotherapy
 Initial studies - Injecting animals with Aβ → good Ab response → cleared amyloid
plaques from brain
 Human studies prematurely ceased (2002) → development of brain inflammation
(Meningoencephalitis) in 6%
 BUT- Evidence  Removed amyloid plaque from the brain
 Idea of active immunisation not abandoned – several pharmaceutical companies
early phases of developing new active vaccines

Passive immunization
Monoclonal antibodies
How to avoid meningoencephalitis symptoms ?

Mechanism Of Action - BAPINEUZUMAB

 Several mAb’s have been studied  Bapineuzumab and Gantenerumab
 Stopped prematurely  Lack of perceived efficacy
 Subgroups did show benefits leading to further studies
 Lack of efficacy  Underdosing
 Recently restarted studies  Gantenerumab in the same patient group
 Larger doses

 Several active ongoing studies
 Some early positive results– Solanezumab, Crenezumab & Adecanumab
 Phase 3 Solanezumab: failed to meet primary endpoints and slow cognitive decline in
AD patients. Trials of this drug are now continuing in prodromal AD patients (the A4
study) – higher doses extending for 3 years
 Phase 3 Adecanumab studies will run until 2022
 Phase 3 Crenezumab studies are still recruiting worldwide

Most patients reported Adverse Effects
94 % Bapineuzumab
90 % Placebo
90 % mild to moderate
in severity
Back pain 12.1% vs 5.5% Weight loss 6.5% vs 1.8%
Anxiety 11.3% vs 3.6% Paranoia 6.5% vs 0.9%
Vomiting 9.7% vs 3.6% Skin laceration 5.6 % vs 2.7%
Vasogenic Edema 9.7% vs 0% Gait disturbance 5.6% vs 1.8%
Hypertension 8.1% vs 3.6% Muscle spasms 5.6 % vs 0.9%
AEs >2 times as often as placebo rate and seen in >5% of bapineuzumab patients
Safety Results

Anti-amyloid strategies
Reducing production
BACE inhibitors such as Lanabecestat
prevent the production of beta-
amyloid.

Methylthioninium Chloride (Methylene Blue)
 First drug targeting Tau
 Derived from the dye used to stain NFT’s
 Inhibits Tau aggregation
 Phase 2 study showed cognitive benefits
 Phase 3 trial for mild-moderate AD - finished February 2016 – failed to slow cognitive or
functional
 30% drop-out due to side-effects
 2nd generation compound (TRx0237) currently in Phase 3 trials for AD

Tau Therapies
 Mouse and primate models of AD show amyloid plaques
 Respond to anti-amyloid therapy
 But no tau pathology like human AD
 Aged dogs develop AD  Aβ and NFT’s
 Tau immunisations  Animal models  Reduction Tau & clinical benefits
 Small number of Tau immunotherapies  phase 1 and 2 testing
 Initial reports No serious adverse effects (still very early)

Tau Therapies
• Lithium inhibits chemical changes in Tau  NFT’s
• Studies on Lithium (Mixed)  Benefit with very low doses in MCI
 Worsening confusion (Studies needed)
External Ca2+ ER Ca2+
Lithium Lithium
NMDA
antagonism
IMP
inhibition
Lowered Intracellular
Ca2+ intrusion from
External stores
Reduced IP3
Lowered Intracellular
Ca2+ intrusion from
Internal stores

Vascular disease and Alzheimer’s
 Larger, longer randomised controlled trials
 Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability
(FINGER study) →preventive study
 Combination of diet, exercise, cognitive training and vascular risk factor monitoring
in an “at risk” population.
 Early 2 year results look promising
 Now expanding to UK, Singapore, China and USA

 Alzheimer’s Prevention Initiative (API) international consortium
 Research in 5000 members  Colombia,South America
 Study on asymptomatic individuals  carry the PS1 mutation
 Using the monoclonal antibody Crenezumab vs. placebo
 This is a five year study and is still recruiting

Glycogen synthase kinase 3 beta (GSK3β)  GSK3β activity
 increased Aβ production & deposits,
 Tau hyperphosphorylation
synaptic damage in AD patients & animal models
(VDAC- Voltage-dependent anion-selective channel)
GSK3β INHIBITORS

Screening in Alzheimer’s Disease
Passive Avoidance Methods
Active Avoidance Methods
Discrimination Learning
Conditioned Response
a) Step down test in Mice & Rat
b) Step through test in rodents
c) Uphill avoidance tests in rats
d) Scopalamine induced amnesia in mice
e) Ibotenic acid-induced impairment of
memory
a) Runway avoidance in rats & mice
b) Shuttle box avoidance test
c) Jumping avoidance test
a) Spatial habituation learning
b) Spatial discrimination test in rodents
c) Spatial learning test in water maze
d) Olfactory learning in rats
a) Conditioned nictitating
membrane response in
rabbits

SUMMARY
 AD - Most debilitating diseases affecting the old age.
 Pathology - Amyloid beta protein & Tau protein.
 No cure – Delay progression
 Approved drugs – AChE & NMDA receptor inhibitors.

WORLD ALZHEIMER’S DAY
SEPTEMBER 21ST
2019 Theme – ENDING STIGMA

“Even though helpful
medication exists, there’s
still no cure,
and we have to keep
fighting

References
1) Goodman & Gilman’s The Pharmacological Basis of Therapeutics 13th ed.
2) Bertram G Katzung Basic & Clinical Pharmacology 14th ed.
3) Rang & Dale’s Pharmacology 9th ed.
4) Lippincott’s Illustrated Reviews Pharmacology 5th ed.
5) KD Tripati Essentials of Medical Pharmacology 7th ed.
6) R S Satoskar Pharmacology and Pharmacotherapeutics 25th ed
7) Sharma & Sharma’s Principles of Pharmacology 3rd ed.
8) Dr S K Srivastava Pharmacology for MBBS 1st ed.
9) M.N.Ghosh fundamentals of experimental pharmacology 6th ed.
10) Bikash medhi & ajay Prakash Practival manual of exp. & clinical pharmacology
11) S K Gupta Drug Screening Methods 3rd ed.
12) N.S. Parmar Screening Methods in Pharmacology 4th reprint
13) Alzheimer’s Disease: Genes Sapeck Agrawal Gaithersburg, MD, USA DOI //dx.doi.org/10.13070/mm.en.7.2226

Alzheimer's disease

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