Degenerative Nerve Disease

Degenerative Disease of the Cortex

Alzheimer's disease (AD) is a degenerative disease afflicting neurons of the cerebral cortex. Loss of cortical neurons initially manifests as impairment of higher cerebral function which progresses to severe memory loss with disorientation. The final outcome of AD involves the complete loss of higher cerebral function which at autopsy presents as massive cerebral atrophy. These symptoms do not usually manifest in patients before they reach the age of 50. With the aging population, AD has turned into the most common cause of dementia in the elderly.

AD is thought to be sporadic in causality although familial cases do exist. Currently, the accumulation of [Page 482]two major proteins has been implicated in leading to the development of AD: Aβ amyloid and tau protein. Aβ amyloid is an integral membrane protein which can be cleaved into two species, one of 40 amino acids in length, the other of 42. Although the method by which Aβ amyloid induces neuronal death is unknown, Aβ amyloid 40 is thought to be protective against AD induced by Aβ amyloid 42. Presenilin is a proteolytic enzyme responsible for cleaving and clearing Aβ amyloid protein. Thus, mutations in presenilin are often responsible for a patient's AD. Tau, on the other hand, is a protein normally associated with microtubules in axons of neurons, that serve to facilitate vesicular transport. In the disease state, tau is hyperphosphorylated, its accumlation leads to the formation cytoplasmic neurofibrillary tangles. Aggregates of these proteins in the cortex (frontal, parietal, and temporal lobes) leads to the development of neuritic plaques of twisted neural axons visible upon biopsy.

Because Aβ amyloid is coded for on chromosome 21, genetic predisposition to AD is associated with patients who suffer from Down Syndrome. Almost all patients with trisomy 21 and live into their 40s develop AD. Not only are they almost guaranteed to suffer from AD, because of increased production of Aβ amyloid, but symptoms of dementia also manifest earlier than patients with only two copies of the allele.

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