Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease.

• BACKGROUND: We used a sensitive and specific beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) assay to determine the relationship between BACE1 activity in cerebrospinal fluid (CSF) and markers of APP metabolism and axonal degeneration in early and late stages of Alzheimer disease (AD). OBJECTIVE: To assess CSF BACE1 activity in AD. DESIGN: Case-control and longitudinal follow-up study. SETTING: Specialized memory clinic. Patients Eighty-seven subjects with AD, 33 cognitively normal control subjects, and 113 subjects with mild cognitive impairment (MCI), who were followed up for 3 to 6 years. MAIN OUTCOME MEASURES: Cerebrospinal fluid BACE1 activity in relation to diagnosis and CSF levels of secreted APP and amyloid beta protein (Abeta) isoforms and the axonal degeneration marker total tau. RESULTS: Subjects with AD had higher CSF BACE1 activity (median, 30 pM [range, 11-96 pM]) than controls (median, 23 pM [range, 8-43 pM]) (P =.02). Subjects with MCI who progressed to AD during the follow-up period had higher baseline BACE1 activity (median, 35 pM [range, 18-71 pM]) than subjects with MCI who remained stable (median, 29 pM [range, 14-83 pM]) (P < .001) and subjects with MCI who developed other forms of dementia (median, 20 pM [range, 10-56 pM]) (P <.001). BACE1 activity correlated positively with CSF levels of secreted APP isoforms and Abeta(40) in the AD and control groups and in all MCI subgroups (P < .05) except the MCI subgroup that developed AD. Strong positive correlations were found between CSF BACE1 activity and total tau levels in all MCI subgroups (r >or= 0.57, P

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Aged

Aged

80 and over

Alzheimer Disease

cerebrospinal fluid

enzymology

pathology

Amyloid

adverse effects

physiology

Amyloid Precursor Protein Secretases

cerebrospinal fluid

physiology

Aspartic Endopeptidases

cerebrospinal fluid

physiology

Axons

enzymology

pathology

Biological Markers

cerebrospinal fluid

Case-Control Studies

Enzyme Activation

physiology

Female

Follow-Up Studies

Humans

Longitudinal Studies

Male

Middle Aged

Nerve Degeneration

cerebrospinal fluid

enzymology

pathology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)