Protein markers for Alzheimer disease in the frontal cortex and cerebellum

Verdile, G., Gnjec, A., Miklossy, J., Fonte, J., Veurink, G., Bates, K., Kakulas, B., Mehta, P. D., Milward, E. A., Tan, N., Lareu, R., Lim, D., Dharmarajan, A., & Martins, R. N. (2004) Protein markers for Alzheimer disease in the frontal cortex and cerebellum. Neurology, 63(8), pp. 1385-1392.

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Objective: To compare proteins related to Alzheimer disease ( AD) in the frontal cortex and cerebellum of subjects with early-onset AD (EOAD) with or without presenilin 1 (PS1) mutations with sporadic late-onset AD ( LOAD) and nondemented control subjects.

Methods: Immunohistochemistry, immunoblot analysis, and ELISA were used to detect and assess protein levels in brain.

Results: In EOAD and to a lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and specific increases in Abeta(40) and Abeta(42) ( by ELISA) in the frontal cortex and, in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed reduced levels of PS1 in many of the subjects with EOAD with or without PS1 mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was barely, if at all, detectable. This decrease in PS1 was specific and not attributable solely to neuronal loss because amyloid precursor protein (APP) and the PS1-interacting protein beta-catenin levels were unchanged.

Conclusions: This study shows that in the frontal cortex and cerebellum from Alzheimer disease patients harboring certain presenilin 1 mutations, high levels of amyloid beta are associated with low levels of presenilin 1. The study provides the premise for further investigation of mechanisms underlying the downregulation of presenilin 1, which may have considerable pathogenic and therapeutic relevance.

Impact and interest:

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ID Code: 60797
Item Type: Journal Article
Refereed: Yes
Additional Information: Verdile, G Gnjec, A Miklossy, J Fonte, J Veurink, G Bates, K Kakulas, B Mehta, PD Milward, EA Tan, N Lareu, R Lim, D Dharmarajan, A Martins, RN
Keywords: alzheimers, protein
DOI: 10.1212/01.WNL.0000141848.45315.A6
ISSN: 1526-632X
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 14 Jun 2013 02:04
Last Modified: 07 Oct 2016 01:58

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