Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis–dutch type share a decrease in cerebrospinal fluid levels of amyloid β‐protein precursor

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Abstract
The amyloid β-protein is a 39-42 amino acid peptide that is deposited in senile plaques and in cerebral vessel walls in individuals with Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHW A-D), and, to a much lesser extent, normal aging. It is derived from abnormal proteolytic processing of its parent protein, the amyloid β -protein precursor. Here we show that individuals with the HCHWA-D mutation and clinically manifesting the disease have markedly decreased cerebrospinal fluid levels of soluble amyloid β-protein precursor (0.7 ± 0.4 μg/ml) compared with age-matched normal subjects (3.0 ± 0.2 μg/ml) as determined by quantitative immunoblotting and enzyme-linked immunosorbent assays. Similarly, age-matched patients diagnosed with probable Alzheimer's disease also have decreased cerebrospinal fluid levels of soluble amyloid β-protein precursor (1.0 ± 0.3 μg/ml). These parallel findings suggest a common biochemical marker for these two diseases and further establish the pathogenic relatedness of HCHWA-D and Alzheimer's disease.