Alzheimer's Disease

Afflicts 10% of those over 65 and perhaps half of those over 85
Under certain circumstances, Aβ aggregates into long filaments that cannot be cleared by the body's usual scavenger mechanisms.
These aggregates then form the β-amyloid which make up the neuritic plaque in Alzheimer patients
Multiple cognitive deficits develop manifested by both memory impairment and at least one of the following cognitive disturbances: aphasia (speaking), apraxia (movement), agnosia (senses), disturbances in executive functioning, and significant impairment in social or occupational functioning.
Patients are depressed, anxious, or agitated.
As the disease worsens, patients exhibit uncharacteristic aggression until they become less and less aware of their limitations.
Later stages is characterized by greater confusion, disorientation, and dependency on others
Physical health also begins to deteriorate
The pathogenesis of Alzheimer's begins with the Amyloid Precursor Protin. This is abnormally cleaved at the Aβ42 location, creating a fibrillar Aβ. These fibrillar Aβ proteins form amyloid plaques. The amyloid plaques trigger inflammation and neurofibrillary tangles (NFT's). NFT's ultimately lead to neuron death.
Fibrillar Aβ can induce Mitogen-Activated Protein Kinase (MAPK) leading to tau phosphorylation and hence to NFT's

The most common form of dementia in the elderly is Alzheimer's Disease
Almost 50% of individuals 85 years of age and older will suffer from this disease.
Microscopically, neurons are observed to accumulate neurofibrillary tangles of filaments.
Neuritic plaques are formed in neurons of the hippocampus, neocortex, and amygdala.
These structures consist of neuritic processes surrounding a central amyloid core.
This core consists primarily of an autosomal recessive peptide derived from an amyloid precursor protein (APP).
Hirano bodies, which consist of beaded filaments, accumulate in pyrimidal neurons of the hippocampus of these patients.

In Alzheimer's Disease, neurons express β-amyloid precursor protein (βAPP; 695-770 amino acids).
The enzyme β-secretase cleaves βAPP and generates C99βAPP fragment.
The enzyme, γ-secretase, actived by presenilin-1 and presenilin-2, generates β-amyloid peptide, a 40-amino acid fragment.
However, a 42-amino acid β-amyloid peptide fragment can be generated. Presenilin-1 and presenilin-2 mutations increase the activity of γ-secretase and more long β-amyloid peptide fragments are produced.
Long β-amyloid peptide fragments accumulate and form an amyloid plaque that disrupts Ca2+ regulation, leading to the death of adjacent neurons.
Microglial cells and astrocytes aggregate around the amyloid plaque.
Degenerated neuronal processes surround the amyloid plaque to form a neuritic plaque.
Apolipoprotein ε4 interferes with the removal of long β-amyloid peptide.
Tau, a microtubule-associated protein, facilitates the integrity and transporting function of neurotubules.
In Alzheimer's Disease, the amount and type of tau is modified and the microtubule binding affinity is lost. Consequently, tau pairs accumulate in the cytoplasm of the neuron, impairing its function.

- If one half of the brain is continuously functioning, this can lead to Alzheimer's, b/c alzheimer's leads to losing functioning of one half of the brain.
- In Alzheimer's disease, microglia become phagocytic.

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