Alzheimer's disease is a neurodegenerative disorder with severe dementia. Due to the accumulation of Beta-Amyloid proteins acetyl-choline producing neurons are getting degenerated. Alzheimer's disease is one of the most devastating brain disorders of elderly humans. It is an under-treated and under-recognized disease that is becoming a major public health problem.

1. Alzheimer’s disease
Dr. D. VIJAYRAJA
HEAD
DEPARTMENT OF BIOCHEMISTRY
Rev. JACOB MEMORIAL CHRISTIAN COLLEGE
AMBILIKKAI-624612
ODDANCHATRAM

2. What is Alzheimer's Disease?
Note: Dementia is a syndrome consisting of a number of symptoms that
include loss of memory, judgment, reasoning, changes in mood, behaviour
and communication abilities
• Alzheimer’s disease is an
irreversible, progressive
degenerative disease of the
brain, which slowly destroys
memory and thinking skills.
• It is the most common form
of dementia.

3. PREVALENCE OF AD
• AD is the most common cause of
dementia among people age 65
and older.
• Scientists estimate that around 35
million people worldwide have
dementia in 2010.
• According to 2009 World
Alzheimer's report, dementia
prevalence will nearly double
every 20 years, to 65.7 million in
2030 and 115.4 million in 2050.

4. When was the first case of
Alzheimer’s?
• The disease was first identified
by Dr. Alois Alzheimer in
November 3, 1906. Alzheimer
made the diagnosis on a fifty-
one year old named Frau
Auguste D.
• He described the two hallmarks
of the disease: “Amyloid
plaques" and "Neurofibrillary
Tangles tangles"
Frau Auguste D
Dr. Alois Alzheimer

5. Amyloid plaques
• 42 amino acid A-beta peptide
• Produced from APP by beta/gamma
secretase
• Will self-associate to form amyloid plaques
• Insoluble and resistant to proteolysis once
aggregated
• The plaques trigger an inflammatory
response, neuronal cell death, and gradual
cognitive decline.
Amyloid plaques

9. Amyloid precursor protein (APP) is membrane protein that sits in the
membrane and extends outward. It is though to be important for neuronal
growth, survival, and repair.

10. Enzymes cut the APP into fragments, the most important of which
for AD is called b-amyloid (beta-amyloid) or Aß.

11. Beta-amyloid is “sticky” so the fragments cling together along with
other material outside of the cell, forming the plaques seen in the
AD brain.

12. Neurofibrillary Tangles
Neurofibrillary tangles containing tau
protein
Neurofibrillary tangles
Normally tau protein dephosphorylated by
phosphatases
Binds and stabilizes microtubules normally
Abnormal tau in AD is phosphorylated:
 Fails to bind when phosphorylated
 Paired helical filaments form-tangles
 Axonal transport blocked-degeneration

13. Neurofibrillary
Tangles
Neurons have an internal support structure partly made up of
microtubules. A protein called tau helps stabilize microtubules. In AD,
tau changes, causing microtubules to collapse, and tau proteins clump
together to form neurofibrillary tangles. Slide 18

14. Plaques and neurofibrillary tangles
From Department of Pathology, Virginia Commonwealth University

16. Alzheimer’s Disease

17. The Changing Brain in Alzheimer’s
Disease
Positron-emission tomographic (Pet) Scan
of Normal Brain
Pet Scan of Alzheimer’s Disease Brain

18. There are two main types of AD:
1. Early-onset
2. Late-onset
 Early-onset AD is rare, usually affecting
people aged 30 to 60 and usually running
in families. Researchers have identified
mutations in three genes that cause early-
onset AD.
Age
 Late-onset AD is more common. It usually affects people over
age 65. Researchers have identified a gene that produces a
protein called apolipoprotein E (ApoE). Scientists believe
this protein is involved in the formation of beta-amyloid
plaques.

19. In recent years, scientists have discovered genetic links to AD.
Genetics factors
There are Several genes are
associated with AD:
Mutations in
• Presenilin-1 (PS-1) on
chromosome 14
• Presenilin-2 (PS-2) on
chromosome 1
• APP on chromosome 21
• ApoE on chromosome 19

20. Cellular and Molecular Level
• Oxidative damage from free radical
molecules can injure neurons.
• Homocysteine, an amino acid,
is a risk factor for heart
disease. A study shows that an
elevated level of homocysteine
is associated with increased
risk of AD.
Head Injury, Stroke

21. • Cognitive tests
• EEG
• Scans - MRI, CT, PET
Alzheimer’s disease Diagnosis

22. • Gene therapy for PS1, PS2, APP, ApoE4
• Anti-Inflammatory Agents
– ibuprofen and indomethacin
• Amyloid Vaccine
– Immunization with Ab42 in PDAPP mice
• Secretase (beta and gamma) inhibitors
• Phytonutrient Therapy
– Blueberries
– Green tea
– Resveratrol
– Curcumin
– Pomegranate
AD Treatment

23. OUR BASIC RESEARCH ON AD
Our research mainly focus on
• To find out Mitochondrial dysfunction in Alzheimer’s disease
• To find best inhibitor for BACE1 enzyme
• To reduce A-beta formation and A-beta accumulation
• Pathways of APP cleavage and A-beta transports in AD

24. Thank you