Alzheimer's disease is a progressive neurodegenerative disorder that causes brain cells to die, resulting in cognitive decline. It is the most common cause of dementia. The prevalence of Alzheimer's sharply increases with age, affecting around 5% of those aged 65 and over 90% of those aged 95 and older. The hallmark features of Alzheimer's are amyloid plaques and neurofibrillary tangles in the brain. The amyloid plaques contain beta-amyloid protein, while the tangles are made up of tau protein. Mutations in amyloid precursor protein and presenilin genes alter amyloid processing and increase amyloid-beta production, particularly the more pathogenic amyloid-beta 42 form. Hyperphosphorylated tau disrupts microtub

2.  Loss of intellectual ability with ageand originally defind as presenile
dementia
 Alzheimer's disease is a progressive neurologic disorder that causes
the brain to shrink (atrophy) and brain cells to die.
 Alzheimer's disease is the most common cause of dementia — a
continuous decline in thinking, behavioral and social skills that affects
a person's ability to function independently
Increase the Acetylcholinesterase and decreased the Ach whole basic
phenomenon is called Alzheimer

3.  It prevalence rises sharply with age 5% at 65 to 90% at 95 age
ultimately age related dementia was considered as steady of neurons
through life possibly accelerated falling blood supply associated with
atherosclerosis.
 Studied since mid 1980 have specific genetic molecular mechanism

4.  AD is associated with Brain damage and localized loss of neurons
mainly in the Hippocampus, and Basal ganglia .
 The two main characteristics such amyloid plaques, containing
amorphous extracellular deposits of β- amyloid protein and
neurofibrillary tangles comprising filaments of phosphorylated form of
microtubule –associated with protein {Tau}.
 Tau normally present in healthy person also but very small portion and
amyloid[mutation] precursor main pathogenesis of Alzheimer’s.
 Altered processing of amyloid protein from its precursor (amyloid
precursor protein, APP) has been implicated in the pathogenesis of AD.

5. Aβ plaque accumulation& Tau protein function
Aggregates of Aβ 40,42 of APP Genetic mutations
Protein aggregative form
amyloid plaque
Aβ accumulation would cause neurodegeneration, and whether the damage is done by soluble Aβ monomers or oligomers or
by amyloid plaques. There is evidence that the cells die by apoptosis, although an inflammatory response is also evident.
Expression of Alzheimer’s mutations in transgenic animals
Biochemical stage is Tau, the protein of which the neurofibrillary tangles are composed. Its role in neurodegeneration
is unclear, although similar ‘tauopathies’ occur in many neurodegenerative conditions. Tau is a normal constituent of
neurons, being associated with the intracellular microtubules that serve as tracks for transporting materials along
nerve axons. In AD and other tauopathies, Tau is abnormally phosphorylated by the action of various kinases,
including glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5 (CDK5), and dissociates from
microtubules to be deposited intracellularly as paired helical filaments with a characteristic microscopic appearance.
When the cells die, these filaments aggregate as extracellular neurofibrillary tangles. Tau phosphorylation is enhanced
by the presence of Aβ, possibly by activation of kinases. Conversely, hyperphosphorylated Tau favors the formation of
amyloid deposits. Whether hyperphosphorylation and intracellular deposition of Tau directly harms the cell is not
certain, although it is known that it impairs fast axonal transport, a process that depends on microtubule.

6. APP
sAPP
Growth factor
function
Aβ` Aβ42
AGGREGATION
kinase
Tau-p Tau
phosphatases
Paired helical
filaments
Amyloid
plaque
Processing of APP
AMYLOIDODENIC PATHWAY Processing of APP. The main
‘physiological’ pathway gives rise to sAPP,
which exerts a number of trophic
functions. Cleavage of APP at different
sites gives rise to Aβ, the predominant
form normally being Aβ40, which is
weakly amyloidogenic. Mutations in APP
or presenilin's increase the proportion of
APP, which is degraded via the
amyloidogenic pathway, and also increase
the proportion converted to the much more
strongly amyloidogenic form Aβ42. Clearance of
Aβ is impaired by mutations in the apoE4 gene.
Hyperphosphorylated Tau results in dissociation
of Tau from microtubules, misfolding and
aggregation to form paired helical filaments,
which enhance Aβ toxicity

7.  Memantine
 Acetyl cholinesterase inhibitors
[donepezil, galantamine ,rivastigmine]