 |
||||||||||||||||||||||||||||
 |
||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||
The interest in using amyloid precursor protein derivatives as laboratory markers to help confirm a clinical diagnosis of Alzheimer's disease arises from evidence that cerebral accumulation of the B-amyloid 1-42 (AB42) peptide occurs in many cases of Alzheimer's disease. Alzheimer's disease usually begins in the seventh to ninth decades of life, but an early-onset form is well recognized. The neuropathological hallmarks of Alzheimer's disease are the accumulation of senile plaques and neurofibrillary tangles in the brains of patients with both familial and sporadic forms. Senile plaques contain dense fibrillar deposits of B-amyloid peptides, which is toxic to neurons. Several studies of AB42 in CSF have shown a decrease in the level of this peptide in patients with Alzheimer's disease compared to age-matched normal or neurologic disease control subjects. The probable biological explanation for a decrease in AB42 is that the levels decrease, as the peptide becomes increasingly insoluble and forms deposits in the senile plaques. The amyloid gene encodes a large protein called amyloid precursor protein (APP). Sequential proteolytic cleavages of APP by proteases referred to as beta and gamma secretases results in the formation of two sizes of B-amyloid peptides (AB), containing 40 or 42 amino acids. Mutations in the amyloid precursor protein and 3 different presenilin genes enhance the cellular production of AB42 throughout life by selectively increasing the final cleavage of APP by beta or gamma secretase. Presenilin is believed to act directly or as a cofactor in the cleavage of amyloid by gamma secretase. Mutations in the APP and presenilin genes are responsible for the relatively infrequent autosomal dominant form of early-onset Alzheimer's disease. Another gene, the E4 allele of apolipoprotein E, is a strong genetic risk factor for the development of Alzheimer's disease in individuals in their 60's and 70's. It appears to somehow enhance AB42 aggregation and intracellular deposition. Different sizes of amyloid fragments exist in CSF. Measurement of total B-amyloid fragments does not correlate with the presence of Alzheimer's disease and has no clinical utility. Reference range varies from laboratory to laboratory. CSF levels of B-amyloid 1-42 in CSF are decreased in patients with Alzheimer's disease. Specimen requirement is cerebrospinal fluid. Bloody fluids cannot be tested. |
||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||
|
||
