Tags

Type your tag names separated by a space and hit enter

Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study.
Neurology. 2022 May 31; 98(22):e2282-e2292.Neur

Abstract

BACKGROUND AND OBJECTIVE

Individuals with biomarker evidence of β-amyloid (Aβ) deposition are increasingly being enrolled in clinical treatment trials but there is a need to identify markers to predict which of these individuals will also develop tau deposition. We aimed to determine whether Aβ-positive individuals can remain tau-negative for at least 5 years and identify characteristics that could distinguish between these individuals and those who develop high tau within this period.

METHODS

Tau PET positivity was defined using a Gaussian mixture model with log-transformed standard uptake value ratio values from 7 temporal and medial parietal regions using all participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with flortaucipir PET. Tau PET scans were classified as normal if the posterior probability of elevated tau was less than 1%. Aβ PET positivity was defined based on ADNI cutpoints. We identified all Aβ-positive individuals from ADNI who had normal tau PET more than 5 years after their first abnormal Aβ PET (amyloid with low tau [ALT] group) and all Aβ-positive individuals with abnormal tau PET within 5 years (biomarker AD). In a case-control design, logistic regression was used to model the odds of biomarker AD vs ALT accounting for sex, age, APOE ε4 carriership, Aβ Centiloid, and hippocampal volume.

RESULTS

We identified 45 individuals meeting criteria for ALT and 157 meeting criteria for biomarker AD. The ALT group had a lower proportion of APOE ε4 carriers, lower Aβ Centiloid, larger hippocampal volumes, and more preserved cognition, and were less likely to develop dementia, than the biomarker AD group. APOE ε4, higher Aβ Centiloid, and hippocampal atrophy were independently associated with increased odds of abnormal tau within 5 years. A Centiloid value of 50 effectively discriminated biomarker AD and ALT with 80% sensitivity and specificity. The majority of the ALT participants did not develop dementia throughout the 5-year interval.

DISCUSSION

Aβ-positive individuals can remain tau-negative for at least 5 years. Baseline characteristics can help identify these ALT individuals who are less likely to develop dementia. Conservative Aβ cutpoints should be utilized for clinical trials to better capture individuals with high risk of developing biomarker AD.

Links

PMC Free PDF

Authors+Show Affiliations

Josephs KA
From the Departments of Neurology (K.A.J.), Health Sciences Research (Division of Biomedical Informatics and Statistics) (S.D.W.), and Radiology (J.W.), Mayo Clinic, Rochester, MN.
Weigand SD
From the Departments of Neurology (K.A.J.), Health Sciences Research (Division of Biomedical Informatics and Statistics) (S.D.W.), and Radiology (J.W.), Mayo Clinic, Rochester, MN.
Whitwell JL
From the Departments of Neurology (K.A.J.), Health Sciences Research (Division of Biomedical Informatics and Statistics) (S.D.W.), and Radiology (J.W.), Mayo Clinic, Rochester, MN.

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesAmyloidosisApolipoprotein E4BiomarkersHumansNeuroimagingPositron-Emission Tomographytau Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35314506

Citation

Josephs, Keith A., et al. "Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: an ADNI Study." Neurology, vol. 98, no. 22, 2022, pp. e2282-e2292.
Josephs KA, Weigand SD, Whitwell JL. Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study. Neurology. 2022;98(22):e2282-e2292.
Josephs, K. A., Weigand, S. D., & Whitwell, J. L. (2022). Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study. Neurology, 98(22), e2282-e2292. https://doi.org/10.1212/WNL.0000000000200287
Josephs KA, Weigand SD, Whitwell JL. Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: an ADNI Study. Neurology. 2022 May 31;98(22):e2282-e2292. PubMed PMID: 35314506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study. AU - Josephs,Keith A, AU - Weigand,Stephen D, AU - Whitwell,Jennifer L, Y1 - 2022/03/21/ PY - 2021/5/5/received PY - 2022/2/10/accepted PY - 2022/3/23/pubmed PY - 2022/6/3/medline PY - 2022/3/22/entrez SP - e2282 EP - e2292 JF - Neurology JO - Neurology VL - 98 IS - 22 N2 - BACKGROUND AND OBJECTIVE: Individuals with biomarker evidence of β-amyloid (Aβ) deposition are increasingly being enrolled in clinical treatment trials but there is a need to identify markers to predict which of these individuals will also develop tau deposition. We aimed to determine whether Aβ-positive individuals can remain tau-negative for at least 5 years and identify characteristics that could distinguish between these individuals and those who develop high tau within this period. METHODS: Tau PET positivity was defined using a Gaussian mixture model with log-transformed standard uptake value ratio values from 7 temporal and medial parietal regions using all participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with flortaucipir PET. Tau PET scans were classified as normal if the posterior probability of elevated tau was less than 1%. Aβ PET positivity was defined based on ADNI cutpoints. We identified all Aβ-positive individuals from ADNI who had normal tau PET more than 5 years after their first abnormal Aβ PET (amyloid with low tau [ALT] group) and all Aβ-positive individuals with abnormal tau PET within 5 years (biomarker AD). In a case-control design, logistic regression was used to model the odds of biomarker AD vs ALT accounting for sex, age, APOE ε4 carriership, Aβ Centiloid, and hippocampal volume. RESULTS: We identified 45 individuals meeting criteria for ALT and 157 meeting criteria for biomarker AD. The ALT group had a lower proportion of APOE ε4 carriers, lower Aβ Centiloid, larger hippocampal volumes, and more preserved cognition, and were less likely to develop dementia, than the biomarker AD group. APOE ε4, higher Aβ Centiloid, and hippocampal atrophy were independently associated with increased odds of abnormal tau within 5 years. A Centiloid value of 50 effectively discriminated biomarker AD and ALT with 80% sensitivity and specificity. The majority of the ALT participants did not develop dementia throughout the 5-year interval. DISCUSSION: Aβ-positive individuals can remain tau-negative for at least 5 years. Baseline characteristics can help identify these ALT individuals who are less likely to develop dementia. Conservative Aβ cutpoints should be utilized for clinical trials to better capture individuals with high risk of developing biomarker AD. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/35314506/Characterizing_Amyloid_Positive_Individuals_With_Normal_Tau_PET_Levels_After_5_Years:_An_ADNI_Study_ DB - PRIME DP - Unbound Medicine ER -