The critical need for defining preclinical biomarkers in Alzheimer's disease

Abstract

The increasing number of afflicted individuals with late-onset Alzheimer's disease (AD) poses significant emotional and financial burden on the world's population. Therapeutics designed to treat symptoms or alter the disease course have failed to make an impact, despite substantial investments by governments, pharmaceutical industry, and private donors. These failures in treatment efficacy have led many to believe that symptomatic disease, including both mild cognitive impairment (MCI) and AD, may be refractory to therapeutic intervention. The recent focus on biomarkers for defining the preclinical state of MCI/AD is in the hope of defining a therapeutic window in which the neural substrate remains responsive to treatment. The ability of biomarkers to adequately define the at-risk state may ultimately allow novel or repurposed therapeutic agents to finally achieve the disease-modifying status for AD. In this review, we examine current preclinical AD biomarkers and suggest how to generalize their use going forward.

Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: Implications for object recognition

“…Data from the test phase were computed separately for A and B in three 1-minute bins 1 . Data were analysed using mixed ANOVAs, and significant two-way interactions explored with simple main effects analysis using the pooled error term.…”

“…A problem in treatment of AD is the difficulty of diagnosis; in its early stages it is hard to distinguish from normal aging or Mild Cognitive Impairment (MCI), which does not always progress into AD. Thus current drug therapies are not optimally effective because they are administered only once clear clinical symptoms are manifest [1]. But the neuropathological changes underlying AD begin many years before symptoms emerge [2], meaning early intervention is possible.…”

Application of fatty acid and lipid measurements in neuropsychiatry

“…However, modern scientific approaches help in gathering as much information on the disorder as possible. Those methods are mainly proteomics methods [98][99][100][101][102] but also include metabolomics [103][104][105][106] and transcriptomics [107]. The ideal biomarker for AD should detect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases.…”

Late-Life Vascular Risk Factors and Alzheimer Disease Neuropathology in Individuals with Normal Cognition

“…The preclinical phase of the AD continuum represents a critical opportunity for therapeutic intervention; however, robust methods to detect AD-related pathophysiological changes during life must first be established. Cerebrospinal fluid (CSF) protein assays and neuroimaging (eg positron emission tomography [PET]) are currently the gold standards for the detection of AD neuropathology during life (1,6). The high expense and invasive nature of CSF assays and neuroimaging limit their utility as frontline detection methods, however, resulting in a need for noninvasive and cost-efficient preclinical AD biomarkers (7).…”