Effects of Alzheimer's Disease-Associated Risk Loci on Amyloid-β Accumulation in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients

被引：7

作者：

Laitera, Tiina ^{[1
,2
,3
,4
]}

Paananen, Jussi ^{[5
]}

Helisalmi, Seppo ^{[1
,2
]}

Sarajarvi, Timo ^{[1
,2
,5
]}

Huovinen, Joel ^{[3
,4
]}

Laitinen, Marjo ^{[1
,2
]}

Rauramaa, Tuomas ^{[6
,7
,8
]}

Alafuzoff, Irina ^{[9
]}

Remes, Anne M. ^{[1
,2
]}

Soininen, Hilkka ^{[1
,2
]}

Haapasalo, Annakaisa ^{[10
]}

Jaaskelainen, Juha E. ^{[3
,4
]}

Leinonen, Ville ^{[3
,4
]}

Hiltunen, Mikko ^{[1
,2
,5
]}

机构：

[1] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland

[2] Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland

[3] Univ Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland

[4] Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland

[5] Univ Eastern Finland, Inst Biomed, Yliopistonranta 1E, Kuopio 70210, Finland

[6] Univ Eastern Finland, Inst Clin Med Pathol, Kuopio, Finland

[7] Kuopio Univ Hosp, Dept Pathol, Kuopio, Finland

[8] Kuopio Univ Hosp, Dept Pathol, Kuopio, Finland

[9] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[10] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2017年 / 55卷 / 03期

基金：

芬兰科学院;

关键词：

Alzheimer's disease; amyloid-beta; apolipoprotein E; genome wide association studies; idiopathic normal pressure hydrocephalus; APOLIPOPROTEIN-E; COGNITIVE IMPAIRMENT; PRECURSOR PROTEIN; BIOPSY; SUSCEPTIBILITY; MECHANISMS; BIOMARKERS; DIAGNOSIS; SECRETASE; TAU;

D O I：

10.3233/JAD-160554

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition featuring characteristic symptoms, ventriculomegaly, and normal or slightly elevated cerebrospinal fluid pressure. In Alzheimer's disease (AD) patients, diffuse aggregates of amyloid-beta (A beta) and neurofibrillary hyperphosphorylated tau are detected in the neocortex of the brain, while similar accumulation of A beta is also detected in iNPH. Recent genome-wide association studies have identified several novel risk loci for AD, potentially affecting A beta-related cellular processes. Apart from the apolipoprotein E epsilon 4 allele (APOE4), the risk effect of single loci is low, emphasizing the importance of the polygenic risk score approach when assessing the combined effects. Objective: To study the effects of AD-associated individual and polygenic risk score of single nucleotide polymorphisms (SNPs) on the accumulation of A beta in the brain samples of iNPH patients. Methods: A sample set of frontal cortex biopsies from 188 iNPH patients were divided into two groups according to the A beta pathology. After the genotyping of the AD-associated risk loci, polygenic risk score was calculated for each iNPH patient and subsequently analyzed in relation to A beta deposition. Results: Apart from the APOE4, none of the SNPs revealed a statistically significant effect on the accumulation of A beta in iNPH. Also, the non-APOE4 polygenic risk score did not associate with A beta deposition. Conclusion: Novel AD-associated risk genes have no significant effect on A beta accumulation in the brain of iNPH patients. However, APOE4 affects the A beta deposition in the brain of iNPH and AD patients in a similar manner.

引用

页码：995 / 1003

页数：9

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