CEREBROSPINAL-FLUID LEVELS OF AMYLOID BETA-PROTEIN IN ALZHEIMERS-DISEASE - INVERSE CORRELATION WITH SEVERITY OF DEMENTIA AND EFFECT OF APOLIPOPROTEIN-E GENOTYPE

Alzheimer's disease (AD) is characterized by formation in brain of neu rofibrillary tangles and of amyloid deposits. The major protein compon ent of the former is tau, while the latter are composed of amyloid bet a-peptides (A beta), which are derived by proteolytic cleavage of the amyloid beta-protein precursor (APP). Both tau and various secretory A PP derivatives including A beta and APP(S) are present in human cerebr ospinal fluid (CSF). To investigate whether clinical signs of AD are p aralleled by changes in CSF levels of these proteins, we correlated qu antitative measures of dementia severity with CSF concentrations of A beta, of APP(S), and of tau. We found that levels of A beta in CSF of AD patients were inversely correlated both to cognitive and to functio nal measures of dementia severity. In contrast, levels of APP(S) and o f tau did not correlate with dementia severity. Apolipoprotein E (apoE ) genotype did not influence CSF levels of A beta, APP(S), or tau, whi ch were similar among AD patients with Apo E epsilon 3/3, epsilon 3/4, and epsilon 4/4 alleles. These data indicate that CSF levels of A bet a decrease with advancing severity of dementia in AD and suggest that they are independent of a patient's Apo E genotype.