Neuroimaging Biomarkers for Alzheimer’s Disease

Abstract

Currently, over five million Americans suffer with Alzheimer’s disease (AD). In the absence of a cure, this number could increase to 13.8 million by 2050. A critical goal of biomedical research is to establish indicators of AD during the preclinical stage (i.e. biomarkers) allowing for early diagnosis and intervention. Numerous advances have been made in developing biomarkers for AD using neuroimaging approaches. These approaches offer tremendous versatility in terms of targeting distinct age-related and pathophysiological mechanisms such as structural decline (e.g. volumetry, cortical thinning), functional decline (e.g. fMRI activity, network correlations), connectivity decline (e.g. diffusion anisotropy), and pathological aggregates (e.g. amyloid and tau PET). In this review, we survey the state of the literature on neuroimaging approaches to developing novel biomarkers for the amnestic form of AD, with an emphasis on combining approaches into multimodal biomarkers. We also discuss emerging methods including imaging epigenetics, neuroinflammation, and synaptic integrity using PET tracers. Finally, we review the complementary information that neuroimaging biomarkers provide, which highlights the potential utility of composite biomarkers as suitable outcome measures for proof-of-concept clinical trials with experimental therapeutics.

Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease

“…Pathological tau deposition represents another key biomarker of AD [ 45 , 46 ]. The development of selective tau tracers, such as the most extensively used tracer 18 F-Flortaucipir [ 47 ], allows researchers to investigate regional distribution of tau pathology in the living human brain [ 46 , 48 , 49 ]. In the preclinical stage, the relationship between the symptoms of SCD and tau burden has been reported by Swinford and colleagues [ 50 ].…”

Bridging the Gap Between Fluid Biomarkers for Alzheimer’s Disease, Model Systems, and Patients

“…Studies ( Kuhl et al, 1982 ) have demonstrated that in older ages cerebral glucose metabolism decreases, and that the MTLs, the posterior cingulate cortex and the precuneus show the least age-dependent change. These regions express significant hypometabolism in AD ( Márquez and Yassa, 2019 ), and Mosconi et al (2008) showed that FDG-PET could be used to differentiate healthy subjects from AD patients with 98 to 99% specificity. Recent work by ADNI 2 PET Core has examined how FDG-PET and amyloid PET can be combined to track progression of AD.…”

Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa

“…Using other methods to diagnose the different types of dementia will require neuroimaging technology progress, such as positron emission tomography (PET) and magnetic resonance imaging [42]. The different imaging model not only provides complementary information but also the spatial distribution of the measured value can provide abundant information [43]. To some extent, the development of detection technology has broadened the range of biomarkers.…”

“…The National Institute on Aging 2018 Alzheimer's Disease Research Summit "road to treatment and prevention" made an important recommendation to carry out precision medical research in the field of AD. The integration of artificial intelligence and neuroimaging data with other omics data will be the key to progress in the field of AD treatment [43]. In addition to biological factors (such as genetics, CSF and blood proteomics) and AD medical risk factors (such as hypertension, diabetes, obesity, and depression), we can also focus on national factors that may be related to the onset, diagnosis time between different ethnic groups, clinical manifestations and differences between AD [54].…”