Lysosome-associated membrane protein 1 (LAMP-1) in Alzheimer's disease.
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 betaA-peptide immunization. These findings support the participation of lysosomes in betaA-amyloid and, probably, in hyperphosphorylated tau turnover in AD.
Barrachina
M
M
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.
Maes
T
T
Buesa
C
C
Ferrer
I
I
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides / Q000276:immunology; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005455:Fluorescent Antibody Technique; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007114:Immunization; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; D052118:Lysosomal-Associated Membrane Protein 1; D012333:RNA, Messenger