Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

Abstract

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

Distinct BOLD variability changes in the default mode and salience networks in Alzheimer’s disease spectrum and associations with cognitive decline

“…Firstly, our study was cross-sectional. Longitudinal studies would be interesting to track the variability changes along disease progression by comparing with their normal trajectories across the human life span 50,51 . Secondly, how frequency and network specific variability relates to disease markers (e.g., amyloid and tau) remain unclear.…”

Association of cerebrospinal fluid α‐synuclein with total and phospho‐tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

“…In conclusion, we believe that CSF α-syn could represent an additional molecular candidate biomarker to be integrated in the expanding biomarker array needed to accurately stratify cohorts (biomarker-guided) of individuals according to existing and relevant AD-and other ND-associated pathophysiological pathways. From a translational perspective, this enhanced biomarker guidance is expected to substantially optimize the basis to develop and enhance effective targeted therapeutic strategies for the efficient treatment of the individual subject, in line with the evolving precision medicine paradigm (Hampel et al, 2017(Hampel et al, , 2016(Hampel et al, , 2018(Hampel et al, , 2018.…”

<p>Alzheimer’s Disease – Why We Need Early Diagnosis</p>

“…While several reviews have considered the benefits and challenges of an early diagnosis of Alzheimer's disease, 45,48,49 a greater focus of the current review is placed on how early diagnosis can be used to identify those at risk for or with mild cognitive impairment to prevent or delay the onset of Alzheimer's disease and subsequent dementia.…”