Dataset Information

Amyloid-? misfolding as a plasma biomarker indicates risk for future clinical Alzheimer's disease in individuals with subjective cognitive decline.

ABSTRACT:

Background

We evaluated A? misfolding in combination with A?_42/40 ratio as a prognostic tool for future clinical progression to mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD) in individuals with subjective cognitive decline (SCD).

Methods

Baseline plasma samples (n?=?203) from SCD subjects in the SCIENCe project and Amsterdam Dementia Cohort (age 61?±?9?years; 57% male, mean follow-up time 2.7?years) were analyzed using immuno-infrared-sensor technology. Within 6?years of follow-up, 22 (11%) individuals progressed to MCI or dementia due to AD. Sensor readout values >?1646?cm^-?1 reflected normal A? folding; readouts at ??1646?cm^-?1 reflected low and at -?1 high misfolding. We used Cox proportional hazard models to quantify A? misfolding as a prognostic biomarker for progression to MCI and dementia due to AD. The accuracy of the predicted development of MCI/AD was determined by time-dependent receiver operating characteristic (t-ROC) curve analyses that take individual follow-up and conversion times into account. Statistical models were adjusted for age, sex, and APOE?4 status. Additionally, plasma A?_42/40 data measured by SIMOA were statistically analyzed and compared.

Results

All 22 patients who converted to MCI or AD-dementia within 6?years exhibited A? misfolding at baseline. Cox analyses revealed a hazard ratio (HR) of 19 (95% confidence interval [CI] 2.2-157.8) for future conversion of SCD subjects with high misfolding and of 11 (95% CI 1.0-110.1) for those with low misfolding. T-ROC curve analyses yielded an area under the curve (AUC) of 0.94 (95% CI 0.86-1.00; 6-year follow-up) for A? misfolding in an age, sex, and APOE?4 model. A similar model with plasma A?_42/40 ratio yielded an AUC of 0.92 (95% CI, 0.82-1.00). The AUC increased to 0.99 (95% CI, 0.99-1.00) after inclusion of both A? misfolding and the A?_42/40 ratio.

Conclusions

A panel of structure- and concentration-based plasma amyloid biomarkers may predict conversion to clinical MCI and dementia due to AD in cognitively unimpaired subjects. These plasma biomarkers provide a noninvasive and cost-effective alternative for screening early AD pathological changes. Follow-up studies and external validation in larger cohorts are in progress for further validation of our findings.

SUBMITTER: Stockmann J

PROVIDER: S-EPMC7761044 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Amyloid-β misfolding as a plasma biomarker indicates risk for future clinical Alzheimer's disease in individuals with subjective cognitive decline.

Stockmann Julia J Verberk Inge M W IMW Timmesfeld Nina N Denz Robin R Budde Brian B Lange-Leifhelm Julia J Scheltens Philip P van der Flier Wiesje M WM Nabers Andreas A Teunissen Charlotte E CE Gerwert Klaus K

Alzheimer's research & therapy 20201224 1

<h4>Background</h4>We evaluated Aβ misfolding in combination with Aβ<sub>42/40</sub> ratio as a prognostic tool for future clinical progression to mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD) in individuals with subjective cognitive decline (SCD).<h4>Methods</h4>Baseline plasma samples (n = 203) from SCD subjects in the SCIENCe project and Amsterdam Dementia Cohort (age 61 ± 9 years; 57% male, mean follow-up time 2.7 years) were analyzed using immuno-infrared-senso ...[more]

PMID: 33357241

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