Topological Biomarker of Alzheimer’s Disease

Abstract

For years, it has been assumed that the cerebral accumulation of pathologic protein forms is the main trigger of Alzheimer's disease (AD) pathology; however, recent studies revealed strong evidences that the alternations in synaptic activity precede and affect the homeostasis of amyloid-beta and tau, both of which aggregate during AD. Given that the neuropathological changes, characteristic for AD, start decades before the onset of the first symptoms, when alternations become irreversible, it is crucial to find a biomarker that can detect the preclinical signs of disease, presumably synaptic dysfunction of specific cerebral areas. Here is presented a novel, a high potential neuroimaging biomarker that can detect the postsynaptic dysfunction of specific neural substrate located in medial prefrontal cortex (mPFC) during sensory gating processing of a simple auditory stimulus. The magnetoencephalography-based localization of mPFC gating activation has the potential not only to detect symptomatic AD but also to become a predictor of cognitive decline related to the pathophysiological processes of AD, both at the individual level. The strengths of proposed biomarker lie in the simplicity of using a binary value, i.e., activated or not activated a neural generator along with its potential to follow the evolution of the pathophysiological process of disease from preclinical phase. The novel biomarker does not require estimation of uniform cutoff levels and standardization processes, the main problems of so far proposed biomarkers. Ability to individually detect AD pathology during putative preclinical and clinical stages, absolute noninvasiveness, and large effect size give this biomarker a high translation capacity and clinical potential.

Triple Model of Auditory Sensory Processing: a Novel Gating Stream Directly Links Primary Auditory Areas to Executive Prefrontal Cortex

“…However, the functional mapping of cortical sensory processing pathways remains an ongoing quest. Recent neuroimaging studies investigating the spatio-temporal characteristic of the early auditory sensory processing provide strong evidence for the existence of a third, very fast sensory processing stream that directly links the executive prefrontal brain centers with the primary sensory areas [12][13][14][15][16] . This novel processing stream supports the phenomenon known as sensory gating.…”

Attention modulates topology and dynamics of auditory sensory gating

“…Sensory gating deficits are associated with the pathophysiology of bipolar disorder (Wang et al, ), post‐traumatic stress disorder (Neylan et al, ), Parkinson's disease (Teo et al, ), Huntington's disease (Uc, Skinner, Rodnitzky, & Garcia‐Rill, ), and depression (Wang et al, ). Although abnormalities in extracranially measured auditory gating responses are recognized as a well‐established trait in patients with schizophrenia (Adler et al, ; Bramon, Rabe‐Hesketh, Sham, Murray, & Frangou, ; Patterson et al, ), recent studies have revealed gating source topology modulation to have a high potential to be an individual biomarker for the detection of Alzheimer's disease (Josef Golubic, ; Josef Golubic et al, ), which may provide a unique opportunity to detect physiological changes associated with the disease before symptoms occur.…”