Dataset Information

Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.

ABSTRACT:

Background

Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181.

Methods

Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to examine the relation between AD PRSs, constructed based on findings in recent genome-wide association studies, and plasma p-tau181, using linear regression models. Analyses were performed in the total sample (n?=?818), after stratification on diagnostic status (CU (n?=?236), MCI (n?=?434), AD dementia (n?=?148)), and after stratification on A? pathology status (A? positives (n?=?322), A? negatives (n?=?409)).

Results

Associations between plasma p-tau181 and APOE PRSs (p?=?3e^-18-7e^-15) and non-APOE PRSs (p?=?3e^-4-0.03) were seen in the total sample. The APOE PRSs were associated with plasma p-tau181 in all diagnostic groups (CU, MCI, and AD dementia), while the non-APOE PRSs were associated only in the MCI group. The APOE PRSs showed similar results in amyloid-? (A?)-positive and negative individuals (p?=?5e^-5-1e^-3), while the non-APOE PRSs were associated with plasma p-tau181 in A? positives only (p?=?0.02).

Conclusions

Polygenic risk for AD including APOE was found to associate with plasma p-tau181 independent of diagnostic and A? pathology status, while polygenic risk for AD beyond APOE was associated with plasma p-tau181 only in MCI and A?-positive individuals. These results extend the knowledge about the relation between genetic risk for AD and p-tau181, and further support the usefulness of plasma p-tau181 as a biomarker of AD.

SUBMITTER: Zettergren A

PROVIDER: S-EPMC7792087 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.

Zettergren Anna A Lord Jodie J Ashton Nicholas J NJ Ashton Nicholas J NJ Benedet Andrea L AL Karikari Thomas K TK Lantero Rodriguez Juan J Snellman Anniina A Suárez-Calvet Marc M Proitsi Petroula P Zetterberg Henrik H Blennow Kaj K

Alzheimer's research & therapy 20210108 1

<h4>Background</h4>Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a bioma ...[more]

PMID: 33419453

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Dataset Information

Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.

Background

Methods

Results

Conclusions

Publications

Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.

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