Journal
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 32, Issue 5, Pages 505-516Publisher
WILEY
DOI: 10.1111/j.1365-2990.2006.00756.x
Keywords
Alzheimer's disease; beta A-amyloid; LAMP-1; lysosome; neurofibrillary tangle; tau
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Lysosome-associated membrane protein 1 (LAMP-1) is a glycoprotein highly expressed in lysosomal membranes. The present study was initiated to test LAMP-1 mRNA and protein levels in post mortem frontal cortex (area 8) of Alzheimer's disease (AD) stages I-IIA/B and stages V-VIC of Braak and Braak, compared with age-matched controls. TaqMan PCR assays and Western blots demonstrated upregulation of LAMP-1 mRNA and protein in the cerebral cortex in ADVC. In addition, immunohistochemical studies have shown increased LAMP-1 immunoreactivity in neurones, and in glial cells surrounding senile plaques, in AD cases. Interestingly, LAMP-1 immunoreactivity has little correlation with phosphorylated tau deposition and neurofibrillary tangles (NFTs), as neurones with NFTs were rarely LAMP-1 immunoreactive. In contrast, LAMP-1 expression was enhanced in neurones with granulovacuolar degeneration. Finally, LAMP-1 occurred in microglia and multinucleated giant cells in one AD case in whom amyloid burden was cleared following beta A-peptide immunization. These findings support the participation of lysosomes in beta A-amyloid and, probably, in hyperphosphorylated tau turnover in AD.
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