Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia.
Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.
Emanuele
Enzo
E
Molecular Medicine Laboratory, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Peros
Emmanouil
E
Tomaino
Carmine
C
Feudatari
Enrica
E
Bernardi
Livia
L
Binetti
Giuliano
G
Maletta
Raffaele
R
Micieli
Giuseppe
G
Bruni
Amalia C
AC
Geroldi
Diego
D
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics; D002544:Cerebral Infarction / Q000097:blood / Q000150:complications / Q000235:genetics; D015140:Dementia, Vascular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D020766:Intracranial Embolism / Q000097:blood / Q000150:complications / Q000235:genetics; D007558:Italy; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics; D008297:Male; D008970:Molecular Weight; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012016:Reference Values; D012307:Risk Factors
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D020033:Protein Isoforms