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P2‐070: Changes in plasma based biomarkers in Alzheimer's disease, mild cognitively impaired and aged matched normal controls from the ADNI cohort
Author(s) -
Soares Holly,
Potter William,
Immermann Fred,
Pickering Eve,
Kuhn Max,
Shera David,
Zagouras Panayiotis,
Swenson Frank,
Wan Hong,
Ferm Mats,
Siuciak Judith,
Koroshetz Walter,
Simon Adam,
Lee Virginia,
Buckholtz Neil,
Hu William,
Trojanowski John,
Shaw Leslie
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.960
Subject(s) - alzheimer's disease neuroimaging initiative , apolipoprotein e , cohort , medicine , cerebrospinal fluid , alzheimer's disease , oncology , disease , gastroenterology , psychology
and others recently discovered that BACE1 activity was significantly increased in sporadic AD brains and that the concentrations of both CSF BACE1 enzymatic activity and protein were significantly increased in subjects with amnestic mild cognitive impairment (MCI).We have hypothesized that by using BACE1 as a biomarker candidate in CSF, it may aid in early detection and prediction of AD in the at-risk predementia MCI stage. Lumbar punctures, however, are considered an invasive procedure. It may be difficult to obtain the sample size necessary for biomarker validation studies, or for a broad clinical screening with a diagnostic indicator. Therefore, potential biomarkers from a more accessible source, such as blood plasma, are critical for advancement. In this study,wewanted to understandwhetherBACE in the blood fromMCI andADpatients would be changed.Methods: Therewere at least 100 patients in each group. Clinically, the MCI subjects met Petersen criteria for amnestic MCI and the AD subjects met NINDS-ADRDA criteria for the diagnosis. Control group is composed by age-matched healthy individuals. We used BACE enzymatic activity assay, BACE ELISA, Ab1-x and sAPPb tomeasure BACE enzyme activity, expression levels and reaction product.Results: Both BACE enzyme activity and expression levels are significantly changed in MCI and AD patients compared to healthy agematched controls.Conclusions:To our knowledge, this is the first time blood from MCI and AD patients has been systematically examined for BACE1 functional proteins and enzyme activity, as well as the enzymatic product, sAPPb and total Ab1-x. Here, we report significant changes of BACE1 functional proteins in the blood among subjects with MCI or AD compared to age-matched cognitively normal controls. These finding are highly relevant for the improved hypothesis-driven generation of biomarkers for AD, regarding early detection and prediction, as well as for assessment of mechanisms for amyloid lowering compounds currently in phase II-III clinical trials.