Altered Distribution of the Gangliosides GM1 and GM2 in Alzheimer’s Disease

• Published in: Dementia and geriatric cognitive disorders Vol. 33; no. 2-3; pp. 174 - 188
• Main Authors: Pernber, Z., Blennow, K., Bogdanovic, N., Månsson, J.-E., Blomqvist, M.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2012; S. Karger AG
• Subjects: 1984; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; amyloid precursor protein; beta-protein; binding epitope; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; endogenous seed; Female; Frontal Lobe - metabolism; Frontal Lobe - pathology; Frontotemporal dementia; Frontotemporal Dementia - metabolism; Frontotemporal Dementia - pathology; frontotemporal lobar degeneration; G(M1) Ganglioside - metabolism; G(M2) Ganglioside - metabolism; gamma-secretase; Glycosphingolipids; Humans; Immunohistochemistry; Immunohistochemistry - methods; khann g; lipid; Male; Medical sciences; Medicin och hälsovetenskap; membrane microdomains; Membrane Microdomains - metabolism; Middle Aged; monoclonal-antibody; Myelin Sheath - metabolism; Myelin Sheath - pathology; Nervous system (semeiology, syndromes); Neurologi; Neurology; Neurons - metabolism; Neurons - pathology; Original Research Article; p939; Psychiatry; Psykiatri; rafts; Research Design; senile plaques; Temporal; Temporal Lobe - metabolism; Temporal Lobe - pathology; v34; Immunohistochemistry; Temporal lobe; Frontal lobe; Glycosphingolipids; Alzheimer’s disease; Cortex; Frontotemporal dementia; Nervous system diseases; Cognitive disorder; Alzheimer disease; Cerebral disorder; GM1 ganglioside; Temporal Iobe; Frontal Iobe; Central nervous system disease; Frontal; Degenerative disease; Alzheimer's disease
• ISSN: 1420-8008; 1421-9824; 1421-9824
• DOI: 10.1159/000338181

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder where β-amyloid tends to aggregate and form plaques. Lipid raft-associated ganglioside GM1 has been suggested to facilitate β-amyloid aggregation; furthermore, GM1 and GM2 are increased in lipid rafts isolated from cerebral cortex of AD cases. Aim/Method: The distribution of GM1 and GM2 was studied by immunohistochemistry in the frontal and temporal cortex of AD cases. Frontotemporal dementia (FTD) was included as a contrast group. Results: The distribution of GM1 and GM2 changes during the process of AD (n = 5) and FTD (n = 3) compared to controls (n = 5). Altered location of the GM1-positive small circular structures seems to be associated with myelin degradation. In the grey matter, the staining of GM1-positive plasma membranes might reflect neuronal loss in the AD/FTD tissue. The GM1-positive compact bundles were only visible in cells located in the AD frontal grey matter, possibly reflecting raft formation of GM1 and thus a pathological connection. Furthermore, our results suggest GM2 to be enriched within vesicles of pyramidal neurons of the AD/FTD brain. Conclusion: Our study supports the biochemical finding of ganglioside accumulation in cellular membranes of AD patients and shows a redistribution of these molecules.