Abstract
The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer’s disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aβ) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aβ, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.
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Abbreviations
- NFTs:
-
Neurofibrillary tangles
- AD:
-
Alzheimer disease
- CSF:
-
Cerebrospinal fluid
- BACE1:
-
β-Site amyloid precursor protein-cleaving enzyme 1
- P-tau:
-
Phosphorylated tau
- T-tau:
-
Total tau
- α-Syn:
-
α-Synuclein
- LRP:
-
Lewy-related pathology
- PiD:
-
Pick’s disease
- PSP:
-
Progressive supranuclear palsy
- CBD:
-
Cortico-basal ganglionic degeneration
- GFAP:
-
Glial fibrillary acidic protein
- sAPP:
-
Soluble amyloid precursor proteins
- SNAP-25:
-
Synaptosome-associated protein 25
- TDP-43:
-
Transactive response DNA-binding protein 43
- hFABP:
-
Heart-type fatty acid-binding protein
- TREM2:
-
Triggering receptor expressed on myeloid cells 2, IP-10, and VILIP-1 is visinin-like protein 1
- MRI:
-
Structural magnetic resonance imaging
- Aβ:
-
Amyloid beta
- miRNA:
-
MicroRNA
- Mab:
-
Monoclonal antibody
- PHF:
-
Paired helical filament
- APP:
-
Amyloid precursor protein
- NfL:
-
Neurofilament Light Chain
- Ng:
-
Neurogranin
- ALS:
-
Sporadic amyotrophic lateral sclerosis
- FTLD:
-
Frontotemporal lobar degeneration
- VCAM1:
-
Vascular cell adhesion protein 1 precursor
- CT:
-
Computed Tomography
- MCI:
-
Mild Cognitive Impairment
- SVM:
-
Support Vector Machine
- IBASPM:
-
Individual Brain Atlas and Statistical Parametric Mapping
- MTL:
-
Medial Temporal Lobe
- PET:
-
Positron Emission Tomography
- SPECT:
-
Single-Photon Emission Computed Tomography
- FDG:
-
Fluorodeoxyglucose
- ECD:
-
Ethyl cysteinate diethylester
- DTI:
-
Diffusion tensor imaging
- ESI:
-
Electrospray ionization
- DIGE:
-
Difference gel electrophoresis
- MRM:
-
Multiple reaction monitoring
- SRM:
-
Selective reaction monitoring
- TMT:
-
Tandem mass tags
- MEG:
-
Magnetoencephalography
- VBM:
-
Voxel-based morphometry
- VBCT:
-
Voxel-based cortical thickness
- ROI:
-
Region of interest
- Ach:
-
Acetylcholine
- ChEIs:
-
Cholinesterase inhibitors
- NMDA:
-
N-methyl-D-aspartate
- DOPA:
-
Dihydroxyphenylalanine
- BOLD:
-
Blood oxygenated level dependent
- DLB:
-
Dementia with Lewy bodies
- rs-fMRI:
-
Resting-state fMRI
- FTD:
-
Frontotemporal dementia
- DVR:
-
Distribution volume ratio
- SUVR:
-
Standardized uptake value ratio
- AI:
-
Artificial intelligence
- ADP:
-
Alzheimer’s disease pathology
- R&D:
-
Research and development
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Acknowledgements
The authors gratefully acknowledge Ravi Pratap Barnwal lab and Gurpal Singh lab members for critical suggestions. Our lab is supported by Science and Engineering Research Board (SERB), Department of Biotechnology (DBT), and the Indian Council of Medical Research (ICMR), Govt. of India grants which are duly acknowledged.
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Rani, S., Dhar, S.B., Khajuria, A. et al. Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer’s Disease. Cell Mol Neurobiol 43, 2491–2523 (2023). https://doi.org/10.1007/s10571-023-01330-y
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DOI: https://doi.org/10.1007/s10571-023-01330-y