1. RECENT ADVANCES IN TREATMENT OF
ALZHEIMER’S DISEASE
PRESENTED BY
• ADHIYAMAN P M,
M.PHARM. 2nd SEMESTER,
DEPT. OF PHARMACOLOGY,
COLLEGE OF PHARMACY-SRIPMS.

2. CONTENTS
INTRODUCTION
PATHOPHYSIOLOGY
TREATMENT
CONCLUSION
BIBLIOGRAPHY
2

3. INTRODUCTION
• Alzheimer’s disease is the most common form of dementia.
• Progressive disease that destroys memory and other important mental
functions.
• Brain cell connections and the cells themselves degenerate and die.
3

4. SYMPTOMS
Cognitive
Mental decline
Delusion
Mental confusion
Forgetfulness
Inability to recognise
common things
Behavioural
Aggression
Personality changes
Restlessness
Lack of restraint
Others
Paranoia
Loneliness
Depression
4

5. PATHOPHYSIOLOGY
Amyloid cascade
hypothesis
Cholinergic
hypothesis
Tau hypothesis
5

6. AMYLOID CASCADE HYPOTHESIS
6

7. CHOLINERGIC HYPOTHESIS
7

8. TAU HYPOTHESIS
Stabilizes microtubules
Destabilized microtubules
8

9. CLASSIFICATION
Cholinesterase
inhibitors:
Tacrine
Rivastigmine
Donepezil
Galantamine
Glutamate
(NMDA)
antagonist:
Memantine
Nootropic
agents:
Piracetam
Miscellaneous
drugs: Ginkgo
biloba
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10. CHOLINESTERASE INHIBITORS
Side effects
Diarrhea
Abdominal pain
Nausea
Vomiting
10

11. NMDAANTAGONIST
Side effects
Constipation
Tiredness
Headache
Dizziness
Drowsiness
Shortness of breath
Hypertension
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12. NOOTROPIC AGENT
• Piracetam
Neuroprotection
Restored neurotransmission Improved neuronal function
Enhanced neuroplasticity
• Side effects
Gastric discomfort
Insomnia
Dizziness
Skin rash
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13. 13
• Ginkgo biloba
Cognition enhancer
Antioxidant
Increase blood flow
Altitude sickness
• Side effects
Increased risk of bleeding
Allergic skin reaction
Gastric discomfort
MISCELLANEOUS DRUG

14. RECENT ADVANCEMENTS
14

15.  Amyloid precursor protein (APP), presenilin (PSEN1) & PSEN2 genes encode APP
metabolism and Aβ generation.
 Overexpression of APP causing cellular and molecular alteration.
 β-site amyloid precursor protein cleaving enzyme(BACE1) involved in the cleavage
of APP.
siRNA - APP targeted gene therapy
CRISPR-Cas9 suppress Aβ associated pathway
GENE THERAPY
15

16. GENE THERAPY
 Apolipoprotein E (APOE) transporter of lipids.
 APOE2, APOE3 and APOE4 which carries different risk percentage and differs due
to presence of cysteine(112) or arginine(158) .
 APOE4 which increase levels of amyloid while APOE2 has a lower amyloid
burden.
 Increase the expression level of APOE2 which prevent Aβ deposition.
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17. AMYLOID (Aβ) IMMUNOTHERAPY
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18. ACTIVE IMMUNIZATION
 VAN1792 - synthetic Aβ which bound saponin adjuvant QS-21 (Phase 2).
 Removal of amyloid plague.
 CAD106, peptide vaccines carrying Aβ N-terminus representing B cell epitope
(Phase 2).
 Enhanced tolerability and safety profiles.
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19. Name of the drugs Stages
Aducanumab Phase 4
ALZ 801 Phase 1
BAN2401 Phase 3
Bapineuzumab Phase 3
Crenezumab Phase 3
Ponezumab Phase 2
Solanezumab Phase 3
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PASSIVE IMMUNIZATION

20. PASSIVE IMMUNIZATION
20

21. PASSIVE IMMUNIZATION
• Bapineuzumab is an lgG1 antibody that
binds fibrillar and soluble Aβ and activates
microglial phagocytosis and (Phase 3).
21

22. Aβ-TARGETING STRATEGIES
• APP processed by α-secretase within Aβ sequence and generate soluble neurotrophic
sAPPα.
• Accumulation of Aβ in brain leads to oxidative stress, neuronal dysfunction.
• Secondary prevention of AD can be made by:
Decreasing the production of Aβ
Stimulation of clearance of Aβ formed
Prevention of aggregation of Aβ into amyloid plaques
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23. • Decreasing Aβ neurotoxicity or inhibiting its aggregation have therapeutic
potentials.
• β-sheet breaker iAβ5p, which showed improved spatial memory and decreased
amyloid plaque deposits (Phase 2).
• Upregulation of α-secretase activity which decrease the amount of APP.
• Deprenyl, increase α-secretase activity by promoting ADAM10 and PKC.
Aβ-AGGREGATION INHIBITORS
α-SECRETASE ACTIVATORS/MODULATORS
23

24. β-SECRETASE INHIBITORS
 BACE1 inhibitor Lowering of brain Aβ40 and Aβ42.
 Decreased APPβ and an increased sAPPα secretion.
 KMI-429 reduce Aβ production (Phase 2).
 BMS-299897 and MRK560 is a γ-secretase inhibitors (Phase 1 & 3).
 γ-secretase modulators, shifting the γ-secretase cutting point to produce shorter,
non-toxic Aβ fragments.
γ-SECRETASE INHIBITORS/MODULATORS
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25. PREVENTION OF PHOSPHORYLATION OF TAU
 Phosphorylation of tau is controlled by different kinases and phosphatases.
 The protein phosphatase (PP)-2A increase dephosphorylation of tau.
 Cyclin-dependent kinase-5 (CDK5) and Glycogen synthase kinase (GSK)-3β which
phosphorylate tau in AD.
 AF267B – inhibit GSK-3β
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26. CONCLUSION
• Current therapies providing temporary improvement and reducing the rate of
cognitive decline.
• Gene therapy appear is a alternative therapeutics strategy.
• Identifying potential therapeutic compounds.
26

27. BIBLIOGRAPHY
Hong-Qi Y, Zhi-Kun S, Sheng-Di C. Current advances in the treatment of Alzheimer’s disease:
Focused on considerations targeting Aβ and Tau. Transl Neurodegener. 2012; 1(21): 2-9.
Marei HE, Althani1 A, Suhonen J, Zowalaty1 ME, Albanna ME, Cenciarelli C, Wang T, Caceci T.
Recent perspective about the amyloid cascade hypothesis and stem cell - based therapy in
the treatment of Alzheimer’s disease. FCDR. 2016; 5: 3-33.
Rang HP, Dale MM, Ritter JM, Flower R, Henderson G. Pharmacology: Neurodegenerative diseases. 9th ed.
Edinburg: Elseveir Ltd; 2020.
Standaert DG, Roberson ED. Treatment of central nervous system degenerative disorders. In: Brunton LL,
Chabner BA, Knollman BC. Goodman & Gilman’s The pharmacological basis of therapeutics. 12th
ed. New York: McGraw - hill medical publishers; 2011.
Thoe ES, Fauzi A, Tang YQ, Chamyuang S, Chia YA. A review on advances of treatment modalities for
Alzheimer’s disease. Life Sci. 2021; 276: 1-15.
Tripathi KD. Essentials of medicinal pharmacology. 8th ed. New delhi: Jaypee medical publishers;
2019. 27

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