Cerebrospinal fluid levels of amyloid β‐protein in alzheimer's disease: Inverse correlation with severity of dementia and effect of apolipoprotein e genotype

Abstract

Alzheimer's disease (AD) is characterized by formation in brain of neurofibrillary tangles and of amyloid deposits. The major protein component of the former is τ, while the latter are composed of amyloid β‐peptides (Aβ), which are derived by proteolytic cleavage of the amyloid β‐protein precursor (APP). Both β and various secretory APP derivatives including Aβ and APP^s are present in human cerebrospinal fluid (CSF). To investigate whether clinical signs of AD are paralleled by changes in CSF levels of these proteins, we correlated quantitative measures of dementia severity with CSF concentrations of Aβ, of APP^s, and of τ We found that levels of Aβ in CSF of AD patients were inversely correlated both to cognitive and to functional measures of dementia severity. In contrast, levels of APP^s and of τ did not correlate with dementia severity. Apolipoprotein E (apoE) genotype did not influence CSF levels of Aβ, APP^s, or τ, which were similar among AD patients with Apo E ε3/3, ε3/4, and ε4/4 alleles. These data indicate that CSF levels of Aβ decrease with advancing severity of dementia in AD and suggest that they are independent of a patient's Apo E genotype.