Peripheral Biomarkers of Alzheimer's Disease

Abstract

Currently available diagnostic tests have moved the field closer to early diagnosis of Alzheimer's disease (AD); however, a definitive diagnosis is made only with the development of clinical dementia and the presence of amyloid plaques and neurofibrillary tangles at autopsy. An ideal antemortem AD biomarker should satisfy the following criteria: the ability to diagnose AD with high sensitivity and specificity as confirmed by the gold standard of autopsy validation; the ability to detect early-stage disease and track the progression of AD; and monitor therapeutic efficacy. AD biomarker technologies currently under development include in vivo brain imaging with PET and MRI (i.e., imaging of amyloid plaques, biochemical assays in cerebrospinal fluid (CSF) and peripheral tissues. CSF biomarkers have received increased attention in the past decade. However, it is unclear whether these biomarkers are capable of early diagnosis of AD, prior to Aβ accumulation, or whether they can differentiate between AD and non-AD dementias. In addition, CSF biomarkers may not lend themselves to diagnostic screening of elderly patients, given the invasiveness of lumbar puncture, inter-laboratory variability in techniques and sample handling, and the circadian fluctuation of CSF components. Although commonly viewed as an abnormality of the brain, AD is a systemic disease with associated dysfunction in metabolic, oxidative, inflammatory, and biochemical pathways in peripheral tissues, such as the skin and blood cells. This has led researchers to investigate and develop assays of peripheral AD biomarkers (a few with high sensitivity and specificity) that require minimally invasive skin or blood samples.

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

“…While this review focuses on studies searching for potential AD biomarkers in blood cells as the most easily accessible cell types, such research in AD is a part of cell-based approaches involving other cell types such as skin fibroblasts and Buccal cells (reviewed in [10,13,14] …”

“…However, the most important advantage of such a hypothesis-driven approach is the possibility that these biomarkers could indicate biologically relevant pathways and processes contributing to the complex pathology of individual patients. Therefore, they could inform in the future about possible individualized therapies in AD patients and about risk factors in those with preclinical AD.While this review focuses on studies searching for potential AD biomarkers in blood cells as the most easily accessible cell types, such research in AD is a part of cell-based approaches involving other cell types such as skin fibroblasts and Buccal cells (reviewed in [10,13,14] …”

Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible

“…[6,[25][26][27][28][29] Furthermore, the skin and brain age together as their intrinsic ageing strongly depends on a similar endocrine environment leading to the suggestion that skin ageing models represent an effective tool for understanding molecular ageing mechanisms of the brain. [30] The notion that skin may reflect a "diagnostic window into the brain" is tempting and the use of alpha-synuclein in skin nerve fibres biopsies to support diagnoses of Parkinson's disease [31,32] and fibroblast-based tests for Alzheimer's disease [33] is currently under investigation.…”

Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

“…Although these are useful to distinguish symptomatic patients from normal controls or other dementias, these CSF biomarkers lack predictive value in preclinical patients, and they are only useful to confirm the clinical diagnosis [84]. Thus, given the brain lipid alterations in AD, lipidomic analysis of lipid derivatives in biological fluids may represent a reliable way to identify non-invasive biomarkers for early AD diagnosis [85].…”