期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 25, 期 2, 页码 373-381出版社
IOS PRESS
DOI: 10.3233/JAD-2011-091153
关键词
BACE1; beta-secretase; cerebrospinal fluid; hippocampus
资金
- Federal Agency of Education and Research (Bundesministerium fuer Bildung und Forschung, BMBF) [01 GI 0102]
- Adelaide and Meath Hospital incorporating the National Children's Hospital (AMNCH)
- Health Service Executive (HSE)
- Trinity College Dublin, Ireland
- Science Foundation Ireland [08/IN.1/B1846]
- National Institute on Aging [NIHRO1AG025888]
- Alzheimer's Association
- Arizona Alzheimer Research Consortium
- NATIONAL INSTITUTE ON AGING [R01AG025888] Funding Source: NIH RePORTER
The enzyme beta-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer's disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-beta(1-42) in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-beta-related processes.
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