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Hindi Essentials of Anatomy as Related to Alzheimers disease: A Review, Extended Abstract
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Copyright: © 2016 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Alzheimer disease (AD) is the sixth leading cause of
death, presently in America. AD is the centre of
preoccupation of not only the scientific community, but
also of the intelligentsia. lzheimer disease (AD) is a
neurodegenerative disorder marked by cognitive and
behavioral impairment that significantly interferes with
social and occupational functioning. It is an incurable
disease with a long preclinical period and progressive
course. In AD, plaques develop in the hippocampus, a
structure deep in the brain that helps to encode memories,
and in other areas of the cerebral cortex that are
involved in thinking and making decisions.
For clinical research, the classification of AD has recently
been divided into 3 phases . First is a presymptomatic
phase during which people are cognitively normal but with
evidence of amyloid deposition with or without other
neuropathological changes. Second is a symptomatic
prodromal phase characterized by mild cognitive
impairment (MCI) with amyloid deposition and more
diverse evidence of neurodegeneration. In Individuals with
MCI due to AD or prodromal AD experience a progressive
cognitive decline greater than expected for their age and
education level but without obvious signs of impaired
function. The third phase occurs when cognitive
impairment worsens and interferes with activities of daily
living. The patient is then diagnosed with dementia and
has a full repertoire of molecular and neurodegenerative
changes.
AD is a progressive disorder with interrelated molecular,
physiological, anatomical, and clinical changes. This
review describes these domains and the progression of
biological changes (genetic, molecular, and cellular) that
underlie AD and their correlation with the clinical
syndrome.
The study of various structures of the brain, their
connections and the pathways involved (anatomy), their
normal functioning (physiology) and how this is subverted,
leading to AD (pathology and pathogenesis), is vital to
understanding comprehensively the complete gamut of
clinical features of the Alzheimer disease. The anatomical
structures, their connections and interplay, as implicated as
having a role in AD, are briefly reviewed in this article.
The functional significance with AD, of each structure is
highlighted. The most common risk genes associated with
AD susceptibility have roles in lipid processing, immune
function, endocytosis, or synaptic integrity . Many genetic
risk factors are associated with late-onset AD (after 65 years
of age or older). Apolipoprotein E is the most well-known
risk factor gene. APOE is involved in cholesterol transport
in CSF and in binding and clearance of beta-amyloid (Aβ) in
the brain . Of its 3 major alleles, the APOE ε4 allele confers
the greatest risk for developing late-onset familial and
sporadic AD, most likely by reducing cholesterol efflux
from neuronal cells and astrocytes, and by binding and
depositing Aβ. The prevalence of this allele is
approximately 15% in the general population and
approximately 40%in patients with AD . The ε2 allele
appears to play a protective role against AD. In addition to
APOE, risk genes associated with lipid processing include
ABCA7, clusterin and sortilin-related receptor L (SORL1).
ABCA7 encodes an adenosine triphosphate (ATP)-binding
cassette transporter and plays multiple roles including
substrate transport across cell membranes, regulation of
amyloid precursor protein (APP) processing, and inhibition
of Aβ secretion . CLU, a major brain apolipoprotein that
reversibly and specifically binds Aβ and appears to act as a
molecular chaperone, influences Aβ aggregation, deposition,
conformation, and toxicity . SORL1 is involved in vesicle
trafficking from the cell surface to the Golgi-endoplasmic
reticulum. It directs APP to endocytic pathways for
recycling and plays an important role in Aβ generation .
Phosphatidylinositol-binding clathrin assembly protein
(PICALM) gene and bridging integrator 1 are implicated in
cell-cell communication and transduction of molecules
across the membrane. CD33 is a member of the sialic-acidbinding
immunoglobulin-like lectins (Siglec) family which
is thought to promote cell-cell interactions and regulate
functions of cells in the innate and adaptive immune
systems . The gene TREM2 has a role in modulating risk for
late-onset AD and heterozygous rare variants are associated
with a significant increase in the risk of AD . TREM2 is an
innate immune receptor expressed on the cell surface of
microglia, macrophages, osteoclasts, and immature dendritic
cells; it triggers the activation of immune responses. CD2-
associated protein is a scaffold/adaptor protein that
associates with proteins involved in receptor-mediated
endocytosis. EPHA1 is a member of the ephrin receptor
subfamily and a membrane-bound protein that plays a role
in cell and axon guidance, cell morphology and motility,
Extended Abstracts Vol 5, Iss1
This work is partly presented at 4th International conference & Exhibition on Neurology and Therapeutics July 27-29,
2015 Rome,Italy Volume 5• Issue 1
and apoptosis and inflammation. Membrane-spanning 4A
gene cluster, which encodes the beta subunit of highaffinity
IgE receptors and complement receptor 1 (CR1),
also plays a role in immune response.
The time course and levels of AD pathology highlight the
connections between the molecular, physiological,
anatomical, and cognitive changes. Dementia associated
with AD is related to the aberrant processing and clearance
of Aβ and tau. Feedback mechanisms associated with
inflammatory responses and oxidative stress set in motion
a cascade of pathological events. Cellular-level events lead
to synaptic dysfunction and neurodegeneration in the
brain. In particular, AD appears to follow the default-mode
network, associated with resting state episodic memory.
Biomarkers for Aβ plaque, neurofibrillary tangles, and
brain atrophy serve as the limited window on biology
