期刊
ALZHEIMERS RESEARCH & THERAPY
卷 14, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13195-022-00990-0
关键词
Plasma biomarkers; Alzheimer's disease; p-tau; Mild cognitive impairment; Dementia
资金
- Lund University
- Alzheimer's Disease Research, a program of the BrightFocus Foundation [A2021013F]
- Swedish Research Council [2016-00906, 2018-02052, 2018-02532, 2017-00915]
- Knut and Alice Wallenberg foundation [2017-0383]
- Medical Faculty at Lund
- Region Skane
- Marianne and Marcus Wallenberg foundation [2015.0125]
- Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
- Swedish Alzheimer Foundation [AF-745911, AF-930655, AF-940046, AF-742881]
- Swedish Brain Foundation [FO20190326, FO2019-0029, FO2017-0243, FO2020-0271]
- Parkinson foundation of Sweden [1280/20]
- Skane University Hospital Foundation [2020O000028]
- Regionalt Forskningsstod [2020-0314, 2020-0383]
- Swedish federal government under the ALF agreement [2018-Projekt0279]
- Stiftelsen Gamla Tjanarinnor [2019-00845]
- EU Joint Programme -Neurodegenerative Disease Research [2019-03401]
- Bundy Academy
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
- Swedish government [ALFGBG-715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- Alzheimer's Association 2021 Zenith Award [ZEN-21-848495]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Swedish Research Council [2018-02052] Funding Source: Swedish Research Council
This study found that the combination of plasma p-tau217 and a brief cognitive composite score is strongly associated with the risk of progression to AD dementia in MCI patients. These findings suggest that these measures could be key components of future prognostic algorithms for early AD.
Background: Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer's disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). Methods: We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-beta 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker. Results: Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75-0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82-0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79-0.95, p = 0 .07). Conclusion: We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD.
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