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Non-invasive Biomarkers for Early Detection of Alzheimer’s Disease: a New-Age Perspective

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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that primarily affects the elderly population. It gradually leads to memory loss, loss of thinking ability, and an overall cognitive decline. However, exhaustive literature is available to suggest that pathological changes in the brain occur decades before the first clinical symptoms appear. This review provides insight into the non-invasive biomarkers for early detection of AD that have been successfully studied in populations across the globe. These biomarkers have been detected in the blood, saliva, breath, and urine samples. Retinal imaging techniques are also reported. In this study, PubMed and Google scholar were the databases employed using keywords “Alzheimer’s disease,” “neurodegeneration,” “non-invasive biomarkers,” “early diagnosis,” “blood-based biomarkers,” and “preclinical AD,” among others. The evaluation of these biomarkers will provide early diagnosis of AD in the preclinical stages due to their positive correlation with brain pathology in AD. Early diagnosis with reliable and timely intervention can effectively manage this disease.

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Data Availability

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

Amyloid-β

APOE4:

Apolipoprotein E4

APP:

Amyloid precursor protein

BHT:

Butylated hydroxytoluene

BBB:

Blood-brain barrier

CSF:

Cerebrospinal fluid

CN:

Cognitively normal

ELISA:

Enzyme-linked immunosorbent assay

FBP-PET:

18F-Florbetapir amyloid-β PET

FTP-PET:

18F-Flortaucipir tau PET

FUPLC-MS:

Fast ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry

GC-MS:

Gas chromatography-mass spectrometry

GFAP:

Glial fibrillary acidic protein

HS score:

Hyperspectral score

1H-NMR:

1H-Nuclear magnetic resonance

LC-FTICR-MS:

Liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry

Lf:

Lactoferrin

MCI:

Mild cognitive impairment

miRNA:

MicroRNA

MCP-1:

Monocyte chemoattractant protein-1

NfL:

Neurofilament light chain

OCT:

Optical coherence tomography

PET:

Positron emission tomography

PS:

Presenilin

PS-OCT:

Polarization-sensitive optical coherence tomography

qRT-PCR:

Quantitative reverse transcription-polymerase chain reaction

rHSI:

Retinal hyperspectral imaging, RNFL

SCD:

Subjective cognitive decline

sCR1:

Soluble complement receptor 1

SD-OCT:

Spectral domain optical coherence tomography

SMC:

Subjective memory complainers

Simoa:

Single-molecule array

TNFR-1:

Tumor necrosis factor-receptor-1

UHPLC-MS:

Ultra-high-performance liquid chromatography-mass spectrometry

UPLC:

Ultra-performance liquid chromatography

VOC:

Volatile organic compound

YKL-40:

Chitinase 3-like-protein-1

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Acknowledgements

The authors are grateful to Mr. Rohit Joshi and Mr. Abbas Jawadwala for their input. We are thankful to the Institute of Chemical Technology, Mumbai, for the facilities and resources.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Mumbai, 400019, Maharashtra, India

    Niyamat M. A. Chimthanawala, Akash Haria & Sadhana Sathaye

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  1. Niyamat M. A. Chimthanawala
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  2. Akash Haria
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  3. Sadhana Sathaye
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Contributions

Writing, literature survey, data analysis—Akash Haria; writing, drafting, conceptualization—Niyamat M.A Chimthanawala; editing, supervision—Sadhana Sathaye. All authors have reviewed and approved the final version of the manuscript prior to submission.

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Correspondence to Sadhana Sathaye.

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Methods

This study was conducted by reviewing papers from reputed journals that have been indexed in databases like PubMed and Google Scholar. The papers chosen were latest in the field of non-invasive biomarkers for early diagnosis of Alzheimer’s disease from 2010 onwards. The keywords selected were “Alzheimer’s disease,” “neurodegeneration,” “non-invasive biomarkers,” “early diagnosis,” “blood-based biomarkers,” “fluid-based biomarkers,” “early-AD,” “mild cognitive impairment,” and “preclinical AD,” among others, as per the scope of the study. Both clinical and preclinical studies of relevance were included. Studies regarding invasive techniques and imaging methods were not included.

Niyamat M. A. Chimthanawala and Akash Haria contributed equally.

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Chimthanawala, N.M.A., Haria, A. & Sathaye, S. Non-invasive Biomarkers for Early Detection of Alzheimer’s Disease: a New-Age Perspective. Mol Neurobiol 61, 212–223 (2024). https://doi.org/10.1007/s12035-023-03578-3

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