A polymorphism in lipoprotein lipase affects the severity of Alzheimer's disease pathophysiology.
Emerging evidences indicate a role for lipoprotein lipase (LPL) in degenerative states. Genetic variations in the LPL gene were previously associated to lipid imbalance and coronary artery disease (CAD) risk and severity, a condition that shares pathological features with common Alzheimer's disease (AD). To evaluate whether these genetic variations associate with the risk and pathophysiology of common AD, autopsy-confirmed patients (242 controls, 153 AD) were genotyped for a PvuII single nucleotide polymorphism (SNP; rs285; referred to as the P+ allele) of LPL. Brain LPL mRNA levels, cholesterol levels, amyloid concentration, senile plaques and neurofibrillary tangles density counts were measured and contrasted with specific LPL genotypes. When adjusted for age and sex, homozygosity for the P+ allele resulted in an odds ratio of 2.3 for the risk of developing AD. More importantly, we report that the presence of the P+ allele of LPL significantly affects its mRNA expression level (n = 51; P = 0.026), brain tissue cholesterol levels (n = 55; P = 0.0013), neurofibrillary tangles (n = 52; P = 0.025) and senile plaque (n = 52; P = 0.022) densities. These results indicate that a common polymorphism in the lipoprotein lipase gene modulates the risk level for sporadic AD in the eastern Canadian population but more importantly, indirectly modulates the pathophysiology of the brain in autopsy-confirmed cases.
Blain
Jean-François
JF
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Aumont
Nicole
N
Théroux
Louise
L
Dea
Doris
D
Poirier
Judes
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001923:Brain Chemistry; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009483:Neuropsychological Tests; D016017:Odds Ratio; D058225:Plaque, Amyloid / Q000473:pathology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D012333:RNA, Messenger; D002784:Cholesterol; D008071:Lipoprotein Lipase