Details

Autor(en) / Beteiligte

• Mäkelä, Mira
• Kaivola, Karri
• Valori, Miko
• Paetau, Anders
• Polvikoski, Tuomo
• Singleton, Andrew B
• Traynor, Bryan J
• Stone, David J
• Peuralinna, Terhi
• Tienari, Pentti J
• Tanskanen, Maarit
• Myllykangas, Liisa

Titel

Alzheimer risk loci and associated neuropathology in a population-based study (Vantaa 85+)

Ist Teil von

• Neurology. Genetics, 2018-02, Vol.4 (1), p.e211-e211

Ort / Verlag

United States: Wolters Kluwer

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• To test the association of distinct neuropathologic features of Alzheimer disease (AD) with risk loci identified in genome-wide association studies. Vantaa 85+ is a population-based study that includes 601 participants aged ≥85 years, of which 256 were neuropathologically examined. We analyzed 29 AD risk loci in addition to ε4, which was studied separately and used as a covariate. Genotyping was performed using a single nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038 variants). Participants with Consortium to Establish a Registry for Alzheimer Disease (CERAD) (neuritic Aβ plaques) scores 0 (n = 65) vs score M + F (n = 171) and Braak (neurofibrillary tangle pathology) stages 0-II (n = 74) vs stages IV-VI (n = 119), and with capillary Aβ (CapAβ, n = 77) vs without (n = 179) were compared. Cerebral amyloid angiopathy (CAA) percentage was analyzed as a continuous variable. Altogether, 24 of the 29 loci were associated (at < 0.05) with one or more AD-related neuropathologic features in either SNP array or imputation data. Fifteen loci associated with CERAD score, smallest = 0.0002122, odds ratio (OR) 2.67 (1.58-4.49) at locus. Fifteen loci associated with Braak stage, smallest = 0.004372, OR 0.31 (0.14-0.69) at locus. Twenty loci associated with CAA, smallest = 7.17E-07, β 14.4 (8.88-20) at locus. Fifteen loci associated with CapAβ smallest = 0.002594, OR 0.54 (0.37-0.81) at locus. Certain loci associated with specific neuropathologic features. , , and associated only with CAA, while and associated only with CapAβ. AD risk loci differ in their association with neuropathologic features, and we show for the first time distinct risk loci for CAA and CapAβ.