• Home
  • Search Results
  • β-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and β-amyloid accumulation.

β-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and β-amyloid accumulation.

The European journal of neuroscience (2010-08-24)
Yan Cai, Kun Xiong, Xue-Mei Zhang, Huaibin Cai, Xue-Gang Luo, Jia-Chun Feng, Richard W Clough, Robert G Struble, Peter R Patrylo, Yaping Chu, Jeffrey H Kordower, Xiao-Xin Yan
ABSTRACT

Alzheimer's disease (AD) is the most common dementia-causing disorder in the elderly; it may be related to multiple risk factors, and is characterized pathologically by cerebral hypometabolism, paravascular β-amyloid peptide (Aβ) plaques, neuritic dystrophy, and intra-neuronal aggregation of phosphorylated tau. To explore potential pathogenic links among some of these lesions, we examined β-secretase-1 (BACE1) alterations relative to Aβ deposition, neuritic pathology and vascular organization in aged monkey and AD human cerebral cortex. Western blot analyses detected increased levels of BACE1 protein and β-site-cleavage amyloid precursor protein C-terminal fragments in plaque-bearing human and monkey cortex relative to controls. In immunohistochemistry, locally elevated BACE1 immunoreactivity (IR) occurred in AD but not in control human cortex, with a trend for increased overall density among cases with greater plaque pathology. In double-labeling preparations, BACE1 IR colocalized with immunolabeling for Aβ but not for phosphorylated tau. In perfusion-fixed monkey cortex, locally increased BACE1 IR co-existed with intra-axonal and extracellular Aβ IR among virtually all neuritic plaques, ranging from primitive to typical cored forms. This BACE1 labeling localized to swollen/sprouting axon terminals that might co-express one or another neuronal phenotype markers (GABAergic, glutamatergic, cholinergic, or catecholaminergic). Importantly, these BACE1-labeled dystrophic axons resided near to or in direct contact with blood vessels. These findings suggest that plaque formation in AD or normal aged primates relates to a multisystem axonal pathogenesis that occurs in partnership with a potential vascular or metabolic deficit. The data provide a mechanistic explanation for why senile plaques are present preferentially near the cerebral vasculature.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-GAD67 Antibody, clone 1G10.2, clone 1G10.2, Chemicon®, from mouse
Sigma-Aldrich
Monoclonal Anti-Parvalbumin antibody produced in mouse, clone PARV-19, ascites fluid
Sigma-Aldrich
Anti-β-Tubulin III antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-Calbindin-D-28K antibody produced in mouse, clone CB-955, ascites fluid
Sigma-Aldrich
Anti-MAP2 antibody, Mouse Monoclonal, clone HM-2, purified from hybridoma cell culture
Sigma-Aldrich
Monoclonal Anti-Tyrosine Hydroxylase antibody produced in mouse, clone TH-16, ascites fluid
Sigma-Aldrich
Anti-APP A4 Antibody, a.a. 66-81 of APP {NT}, clone 22C11, clone 22C11, Chemicon®, from mouse
Sigma-Aldrich
Monoclonal Anti-Collagen, Type IV antibody produced in mouse, clone COL-94, ascites fluid
Sigma-Aldrich
Anti-phospho-Tau (pSer199/202) antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-Glutamate Decarboxylase 65 & 67 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Monoclonal Anti-Growth Associated Protein-43 antibody produced in mouse, clone GAP-7B10, ascites fluid
Sigma-Aldrich
Anti-Synaptophysin Antibody, clone SP15, ascites fluid, clone SP15, Chemicon®
Sigma-Aldrich
Anti-BACE Antibody, CT, Chemicon®, from rabbit
Sigma-Aldrich
Anti-Presenilin-1 (14-33) antibody produced in goat, whole antiserum

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.