Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type share a decrease in cerebrospinal fluid levels of amyloid beta-protein precursor.
The amyloid beta-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 (HCHWA-D), and, to a much lesser extent, normal aging. It is derived from abnormal proteolytic processing of its parent protein, the amyloid beta-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 beta-protein precursor (0.7 +/- 0.4 micrograms/ml) compared with age-matched normal subjects (3.0 +/- 0.2 micrograms/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 beta-protein precursor (1.0 +/- 0.3 micrograms/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.
Van Nostrand
W E
WE
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Wagner
S L
SL
Haan
J
J
Bakker
E
E
Roos
R A
RA
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D000686:Amyloidosis / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics; D001483:Base Sequence; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics; D004247:DNA / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
D016564:Amyloid beta-Protein Precursor; D004247:DNA