Abstract

This article aimed to carry out a narrative literature review of early diagnostic markers of Alzheimer's disease (AD) based on both micro and macro levels of pathology, indicating the shortcomings of current biomarkers and proposing a novel biomarker of structural integrity that associates the hippocampus and adjacent ventricle together. This could help to reduce the influence of individual variety and improve the accuracy and validity of structural biomarker. This review was based on presenting comprehensive background of early diagnostic markers of AD. We have compiled those markers into micro level and macro level, and discussed the advantages and disadvantages of them. Eventually the ratio of gray matter volume to ventricle volume was put forward. The costly methodologies and related high patient burden of "micro" biomarkers (cerebrospinal fluid biomarkers) hinder the implementation in routine clinical examination. In terms of "macro" biomarkers- hippocampal volume (HV), there is a large variation of it among population, which undermines its validity Considering the gray matter atrophies while the adjacent ventricular volume enlarges, we assume the hippocampal to ventricle ratio (HVR) is a more reliable marker than HV alone the emerging evidence showed hippocampal to ventricle ratio predicts memory functions better than HV alone in elderly sample. The ratio between gray matter structures and adjacent ventricular volumes counts as a promising superior diagnostic marker of early neurodegeneration.

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