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Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type share a decrease in cerebrospinal
W E Van Nostrand1, S L Wagner, J Haan
1Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Abstract:
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.
Insights
Individuals with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) and Alzheimer's disease show significantly lower levels of soluble amyloid beta-protein precursor in cerebrospinal fluid, suggesting a shared biomarker.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Amyloid beta-protein is a peptide deposited in the brain in Alzheimer's disease (AD), Down's syndrome, and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D).
- This peptide originates from the amyloid beta-protein precursor (APP) through abnormal processing.
- HCHWA-D is a genetic condition characterized by amyloid deposition in cerebral blood vessels.
Purpose of the Study:
- To investigate cerebrospinal fluid (CSF) levels of soluble amyloid beta-protein precursor (sAPP) in individuals with HCHWA-D and Alzheimer's disease.
- To determine if sAPP levels can serve as a common biochemical marker for HCHWA-D and AD.
- To explore the pathogenic relationship between HCHWA-D and Alzheimer's disease.
Main Methods:
- Quantitative immunoblotting assays were used to measure sAPP levels.
- Enzyme-linked immunosorbent assays (ELISAs) were employed for precise quantification.
- CSF samples from HCHWA-D patients, probable AD patients, and age-matched normal subjects were analyzed.
Main Results:
- Markedly decreased CSF levels of sAPP were observed in individuals with HCHWA-D (0.7 +/- 0.4 µg/ml) compared to normal subjects (3.0 +/- 0.2 µg/ml).
- Similarly, patients with probable Alzheimer's disease showed reduced CSF sAPP levels (1.0 +/- 0.3 µg/ml).
- These findings indicate a significant reduction in soluble APP in the CSF of both patient groups.
Conclusions:
- The parallel decrease in CSF sAPP levels in HCHWA-D and Alzheimer's disease suggests a common biochemical marker.
- These results further support the pathogenic relatedness between HCHWA-D and Alzheimer's disease.
- Soluble amyloid beta-protein precursor levels may be a valuable indicator in the diagnosis and understanding of these neurodegenerative conditions.