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Aging
Alzheimer's
disease is a slow degenerating process, that takes several
decades to develop.
Therefore, aging is the window
that reveals Alzheimer's disease,
but this is not the cause (see Exp Gerontol), stricto
sensus, of the disease.
Normal aging
Pathway of neurofibrillary
degeneration visualized by the presence of pathological
tau proteins in the different brain areas. This
degenerating process starts int the transentorhinal cortex,
then the entorhinal cortex, followed by the hippocampus.
At the biochemical level,this process is systematically
observed in non-demented and demented patients aged over
75 years. This
tau pathology is linked to aging. It shows the vulnerability
of the hippocampal area to a tau pathology. But tau pathology
is no directly expressed as a function of aging, demonstrating
that it is a pathology that appears lately, but not resulting
from aging.In the following figures,
it is shown that this process can be amplified by amyloid
or APP dysfunction, to produce Alzheimer's disease.
ALZHEIMER:
INFRACLINICAL
Alzheimer pathology
starts by a dysfunction of APP, either as a loss of
function, or a gain of toxic function, through the
production of amyloid. Dysfunction of APP is likely
an ubiquitous event, since this protein is in all cells
of all living animals.This dysfunction is represened
as "APP*", meaning that we do not choose if it is due
to APP, APP carboxyterminal fragments or Abeta.APP* weighs
first on the most fragile brain area, which is always
the entorhinal and hippocampal formations, that are always
affected in old age.APP* will intensify tau
pathology of these regions, that in turn will provoke
an extension of tau pathology in other brain areas, like
a chian reaction.
ALZHEIMER'S
DISEASE
There is a dynamic of the
spreading of tau pathology, which depends on numerous
factors. Some of them are risk factors, that accelerate
the disease; others are neuroprotectants.
.Cofactors,
risk factors
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