Examining the association between blood‐based biomarkers and humanpost mortemneuropathology in the University of Kentucky Alzheimer's Disease Research Center autopsy cohort

Abstract

Introduction: Clinically, detection of disease-causing pathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) is limited to magnetic resonance imaging and positron emission tomography scans, which are expensive and not widely accessible. Here, we assess angiogenic, inflammatory, and AD-related plasma biomarkers to determine their relationships with human post mortem neuropathology.Method: Plasma samples were analyzed using a digital immunoassay and pathological evaluation was performed by University of Kentucky Alzheimer's Disease Research Center neuropathologists. The association of plasma markers with neuropathology was estimated via proportional odds and logistic regressions adjusted for age.Results: Included cases (N = 90) showed increased tau/amyloid beta (Aβ)42 ratio, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor A (VEGF-A), and placental growth factor (PlGF) were positively associated with higher level of AD neuropathological change, while higher Aβ42/Aβ40 ratio was inversely associated. Higher PlGF, VEGF-A, and interleukin 6 were inversely associated with chronic cerebrovascular disease, while Aβ42/Aβ40 ratio was positively associated. Discussion: Our results provide support for the continued study of plasma biomarkers as a clinical screening tool for AD and VCID pathology.

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

“…One study following 1456 non-hypertensive patients, of which 232 participants developed hypertension, looked at nine biomarkers, including C-reactive protein (inflammation; found to be a dementia related biomarker), fibrinogen (inflammation/thrombosis), plasminogen activator inhibitor-1 (fibrinolytic potential), aldosterone, renin, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide (neurohormonal functions), homocysteine (oxidant stress; increases both AD and hypertension risk), and urinary albumin/creatinine ration (glomerular endothelial function) in order to understand which biomarkers were associated with hypertension development. 199 The biomarker panel as a whole was significantly associated with the development of hypertension, in particular C-reactive protein, plasminogen activator inhibitor-1, and urinary albumin/creatinine ratio. Indeed, the incidence of hypertension was higher when the number of elevated biomarkers increased.…”

“…Indeed, the incidence of hypertension was higher when the number of elevated biomarkers increased. 199 Biofluid biomarkers, in addition to Hcy itself, have also been identified for HHcy. A recent study looking at blood and CSF samples from 72 patients examined several potential HHcy biomarkers, finding not only that Hcy can be detected within the CSF of patients but also that CSF Hcy concentrations correlated with CSF folate, Sadenosylhomocysteine (SAH), and albumin indicating that these may serve as additional biomarkers to detect HHcy.…”

Specific associations between plasma biomarkers and post-mortem amyloid plaque and neurofibrillary tau tangle loads

“…19 On the other hand, the accuracy of the plasma Aβ42/40 ratio, GFAP, or NfL levels to predict AD pathology seems to be lower than that of p-tau markers, although only few studies have investigated their association with neuropathologic measures of AD pathology. 8,17,20 Another challenge when trying to optimize the use of plasma biomarkers in clinical practice is the lack of comparison among biomarkers in the same population.…”

“…19 On the other hand, the accuracy of the plasma Aβ42/40 ratio, GFAP, or NfL levels to predict AD pathology seems to be lower than that of p-tau markers, although only few studies have investigated their association with neuropathologic measures of AD pathology. 8,17,20…”

“…Nonetheless these studies are scarce, especially those including neuropathological measures. 17,20 This would also allow investigating whether any of these biomarkers might be useful for detecting other common co-pathologies observed in AD patients, such as Lewy bodies or TAR DNA-binding protein 43 (TDP-43). 1,17 When comparing multiple plasma biomarkers, it is equally important to consider the discriminative power of the assays.…”