Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.

Staging amyloid-beta (Aß) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aß pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aß ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aß-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aß therapies.

Subclinical vascular composites predict clinical cardiovascular disease, stroke, and dementia: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed 6814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supineblood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all-cause CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together, and adjustment for conventional risk scores for global CVD, stroke, and dementia. RESULTS: After factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, atherosclerosis, arteriosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of atherosclerosis and arteriosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups. CONCLUSIONS: Subclinical vascular composites of atherosclerosis and arteriosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.

Subclinical Vascular Composites Predict Clinical Cardiovascular Disease, Stroke, and Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) followed 6,814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supine blood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together and adjustment for conventional risk scores for global CVD, stroke, and dementia. Results: After factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, arteriosclerosis, atherosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of arteriosclerosis and atherosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups. Conclusions: Subclinical vascular composites of arteriosclerosis and atherosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.