Apolipoprotein C-I Expression in the Brain in Alzheimer's Disease

Caroline Petit-Turcotte; Sheldon M. Stohl; Uwe Beffert; Jeffrey S. Cohn; Nicole Aumont; Michel Tremblay; Doris Dea; Lin Yang; Judes Poirier; Neil S. Shachter

Neurobiology of Disease (Dec 2001)

Apolipoprotein C-I Expression in the Brain in Alzheimer's Disease

Caroline Petit-Turcotte,
Sheldon M. Stohl,
Uwe Beffert,
Jeffrey S. Cohn,
Nicole Aumont,
Michel Tremblay,
Doris Dea,
Lin Yang,
Judes Poirier,
Neil S. Shachter

Affiliations

Caroline Petit-Turcotte: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Sheldon M. Stohl: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Uwe Beffert: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Jeffrey S. Cohn: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Nicole Aumont: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Michel Tremblay: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Doris Dea: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Lin Yang: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Judes Poirier: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
Neil S. Shachter: McGill Center for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Douglas Hospital Research Center, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3; Division of Preventive Medicine and Nutrition, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH 10-305, New York, New York, 10032-3702; Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7

Journal volume & issue: Vol. 8, no. 6
pp. 953 – 963

Abstract

Read online

The H2 allele of apolipoprotein (apo) C-I is associated with Alzheimer's disease (AD). However, this association is potentially confounded by the linkage disequilibrium of H2 with the ϵ2 and ϵ4 alleles of apoE and of H1 with the ϵ3 allele. To establish plausibility for a direct role for apoC-I in AD, we compared apoC-I and apoE protein and mRNA levels in postmortem specimens of frontal cortex and hippocampus from AD patients with levels in nondemented controls. In H2-allelic individuals (usually also ϵ4 carriers), apoC-I mRNA levels were strikingly lower with AD (by 65%, P < 0.05), but apoC-I protein levels in AD were significantly higher (by 34%, P < 0.05). The opposite direction of the apoC-I mRNA and apoC-I protein level changes in AD in the ϵ4/H2 genotype may reflect decreased clearance of CNS lipoproteins associated with apoE4. In H1/H1 (usually ϵ3/ϵ3) individuals, both apoC-I protein and mRNA were lower in AD. ApoC-I protein levels in hippocampus were nearly twice those in frontal cortex. Immunohistochemistry of hippocampus revealed colocalization of apoC-I protein with the astrocytic marker GFAP. In addition, cultured human astrocytes expressed the mRNA for apoC-I. This study confirms apoC-I expression in the CNS and identifies astrocytes as the source of apoC-I. In addition, it has revealed differences in apoC-I expression based on site, genotype, and disease status that may reflect a role for apoC-I in the pathogenesis of AD.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal