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4 on the Initial Phase of Amyloid ß-Protein Accumulation in the Human Brain
From the Department of Neuropathology,*
Faculty of
Medicine, University of Tokyo, Tokyo; Core Research for Evolutional
Science and Technology,
Japan Science and
Technology Corporation, Kawaguchi; National Institute of Public
Health,
Tokyo; Gunma University School of
Health Sciences,§
Maebashi; Kyoto Prefectural
University of Medicine, Kyoto; and Gunma Cancer
Center,||
Ohta, Japan
Deposition of amyloid ß-protein (Aß), a hallmark of
Alzheimer’s disease, occurs to some extent in the brains of
most elderly individuals. We sought to learn when Aß deposition
begins and how deposition is affected by apolipoprotein
E allele 
4, a strong risk factor for late-onset
Alzheimer’s disease. Using an improved extraction protocol and
specific enzyme-linked immunosorbent assay, we quantified the
levels of Aß40 and Aß42 in the insoluble fractions of brains from
105 autopsy cases, aged 22 to 81 years at death, who
showed no signs of dementia. Aß40 and Aß42 were detected in the
insoluble fractions from all of the brains examined; low levels were
even found in the brains of patients as young as 20 to 30 years of age.
The incidence of significant Aß accumulation increased
age-dependently, with Aß42 levels beginning to rise steeply
in some patients in their late 40’s, accompanied by much
smaller increases in Aß40 levels. The presence of the
apolipoprotein E 4 allele was found to significantly
enhance the accumulation of Aß42 and, to a lesser
extent, that of Aß40. These findings strongly suggest that
the presence of 4 allele results in an earlier onset of Aß42
accumulation in the brain.
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