Blood-Based Biomarkers of Alzheimer's Disease: Challenging but Feasible

Abstract

Blood-based biomarkers present a considerable challenge: technically, as blood is a complex tissue and conceptually, as blood lacks direct contact with brain. Nonetheless, increasing evidence suggests that there is a blood protein signature, and possibly a transcript signature, that might act to increase confidence in diagnosis, be used to predict progression in either disease or prodromal states, and that may also be used to monitor disease progression. Evidence for this optimism comes partly from candidate protein studies, including those suggesting that amyloid-β measures might have value in prediction and those studies of inflammatory markers that consistently show change in Alzheimer’s disease, and partly from true proteomics studies that are beginning to identify markers in blood that replicate across studies and populations.

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

“…Mass spectrometry-based methods, together with innovative tools in progress, are welcomed because they will significantly improve the ability to detect blood markers [127,128]. By simultaneously quantifying the levels of many plasma analytes, biomarker patterns successfully distinguishing AD patients from controls [129] or associated with MCI or AD have been disclosed [130].…”

“…It is also uncertain the existence of only one set of biomarkers for all conceivable uses in AD. It is probable that there will be a group of biomarkers to support AD diagnosis, a different set of molecular markers to predict outcome in AD patients or conversion in MCI, and, probably, another cluster to allow monitoring the evolution of the disease [128].…”

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

“…Therefore, if screening of populations of individuals is to be performed, more suitable, easily accessible tissues would need to be used, also using diagnostic tests at much lower costs compared to brain imaging and cerebrospinal fluid diagnostics of amyloid b and Tau (39)(40)(41). This need for minimally invasive tests could be achieved by targeting surrogate tissues, since it is now well recognized that AD is not a disorder restricted to pathology and biomarkers within the brain only.…”

Genetic risk factor APOEε4 associates with plasma amyloid beta in amnestic mild cognitive impairment and alzheimer’s disease

“…The utility of plasma Aβ as a potential AD biomarker had been assessed in previous studies, but the results have been inconsistent. [38][39][40][41] It is well established that CSF Aβ 42 level decreased in conjunction with the cognitive decline, it has been postulated that plasma Aβ 42 may decrease similarly. 42 Low plasma Aβ 42 at baseline was associated with cognitive decline occurring during follow up.…”