2. INTRODUCTION:
• Alzheimer’s disease (AD) is the commonest progressive, dementing
neurodegenerative disease in elderly, which affects innumerable
people each year, and these numbers are likely to further increase as
the population ages.
• In addition to the financial burden of AD on health care system, the
disease has powerful emotional impact on caregivers and families of
those afflicted.
3. Aloysius ”Alois” Alzheimer
• German psychiatrist
• Described symptoms + pathology
• Neuronal loss
• Plaques
• Tangles
Cipriani et al. (2011) Neurological Sciences, 32(2), 275-279.
1864-1913
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10. PATHOPHYSIOLOGY:
• Alzheimer’s disease is characterized by the loss of neurons and
synapses in the cerebral cortex and certain subcortical regions.
• This loss results in gross atrophy of the affected regions , including
degeneration in the temporal lobe and parietal lobe and parts of frontal
cortex and cingulated gyrus.
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13. • The main pathological hallmarks of Alzheimer’s disease includes:
extracellular deposition of ß-amyloid (Aß) plaques,
intraneuronal neurofibrillary tangles.
Loss of cortical cholinergic neurones in AD probably accounts for
memory impairment.
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17. • Further research, particularly in the genetic domain, led to
identification of APP and Presenilin genes (APP, PSEN1, and
PSEN2) and mutations in these genes as cause of rare forms of
early-onset familial AD.
• On other hand, ε4 allele of apolipoprotein E gene (APOE) has been
recognized as a major risk factor for late-onset AD.
18. • Later, insight into the molecular pathogenesis of AD came
through many transgenic mouse models and tissue culture studies
of AD which led to the proposition of the “amyloid cascade
hypothesis”.
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20. • However, there is growing evidence for the role of additional factors
such as oxidative stress, neuroinflammation, and mitochondrial
dysfunction in the pathogenesis of AD.
21. DIAGNOSIS:
• Detailed patient history
• Information from family and friends
• Laboratory tests like:
Rule out vit B12 and folate deficiency
Rule out hypothyroidism with TFT tests
Blood cell count , serum electrolyte and LFT
• Other diagnostic tests:
CT, PET or MRI scans may aid diagnosis.
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23. • Currently, clinical diagnosis of AD is based on the National Institute of
Neurological Disorders and Stroke—Alzheimer’s Disease and Related
Disorders Association (NINCDS–ADRDA) criteria.
• As the diagnostic criteria is based on the appearance of clinical
symptoms, the time when AD pathology has progressed sufficiently
they fail to detect subjects at preclinical stage.
24. Therefore, there is a growing need for the development of measures
which can detect patients at an early stage.
Various biomarkers in AD can at least partly serve this purpose.
They can detect the patients with AD in their preclinical stage, monitor
the disease progression.
27. • Improving symptomatic decline by improving cognitive
function, daily activities, and behavior
• Current therapy
• Arrests the neurodegenerative molecular process
• Research needed
Primary goals of therapy are:
33. CONCLUSION:
• Cholinergic agents initially improve and transiently maintain cognitive
abilities in patients with mild-to-moderate AD.
• Cognitive abilities worsen over time, indicating treatment does not
stop (but may delay) the progression of AD.
• New treatments that maintain cognitive ability and stop the
progression of AD are needed .
Hinweis der Redaktion
One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques between nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments that the body produces normally. Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.
Neurofibrillary tangles are insoluble twisted fibers found inside the brain's cells. These tangles consist primarily of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. In Alzheimer's disease, however, the tau protein is abnormal and the microtubule structures collapse.