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Neurodegenerative Disorders of Alzheimer, Parkinsonism, Amyotrophic Lateral Sclerosis and Multiple Sclerosis: An Early Diagnostic Approach for Precision Treatment

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Abstract

Neurodegenerative diseases (NDs) are characterised by progressive dysfunction of synapses, neurons, glial cells and their networks. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormalities. The most common neurodegenerative disorders are amyloidosis, tauopathies, a-synucleinopathy, and TAR DNA-binding protein 43 (TDP-43) proteopathy. The protein abnormalities in these disorders have abnormal conformational properties along with altered cellular mechanisms, and they exhibit motor deficit, mitochondrial malfunction, dysfunctions in autophagic–lysosomal pathways, synaptic toxicity, and more emerging mechanisms such as the roles of stress granule pathways and liquid-phase transitions. Finally, for each ND, microglial cells have been reported to be implicated in neurodegeneration, in particular, because the microglial responses can shift from neuroprotective to a deleterious role. Growing experimental evidence suggests that abnormal protein conformers act as seed material for oligomerization, spreading from cell to cell through anatomically connected neuronal pathways, which may in part explain the specific anatomical patterns observed in brain autopsy sample. In this review, we mention the human pathology of select neurodegenerative disorders, focusing on how neurodegenerative disorders (i.e., Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis) represent a great healthcare problem worldwide and are becoming prevalent because of the increasing aged population. Despite many studies have focused on their etiopathology, the exact cause of these diseases is still largely unknown and until now with the only available option of symptomatic treatments. In this review, we aim to report the systematic and clinically correlated potential biomarker candidates. Although future studies are necessary for their use in early detection and progression in humans affected by NDs, the promising results obtained by several groups leads us to this idea that biomarkers could be used to design a potential therapeutic approach and preclinical clinical trials for the treatments of NDs.

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Abbreviations

Aβ:

Amyloid β

AAIC:

Alzheimer’s Association International Conference

AD:

Alzheimer’s disease

ADMC:

Alzheimer Disease Metabolomics Consortium

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

AUC:

AUC: Area under the curve

BA:

Bile acid

BACE1:

β-site APP-cleaving enzyme 1

CAA:

Cerebral amyloid angiopathy

CJD:

Creutzfeldt-Jakob disease

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CV:

Coefficient of variation

ECL:

Electrochemiluminescence

ELISA:

Enzyme-linked immunosorbent assay

GAP-43:

Growth-associated protein-43

HAD:

HIV-associated dementia

HD:

Huntington’s disease

HDL:

High density lipoprotein

IWG-2:

International Working Group 2

LBD:

Lewy body

LRP:

Lipo protein particle

MCI:

Mild cognitive impairment

MND:

Motor neuron disorder

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

MSA:

Multisystem atrophy

MSp:

Mass spectrometry

NDs:

Neurodegenerative diseases

NFL:

Neurofilament light

NFT:

Neurofibrillary tangles

Ng:

Neurogranin

NP:

Neuropathology

NIA-AA:

National Institute of Aging and Alzheimer’s Association

NICE:

The National Institute for Health and Care Excellence

NIH:

National Institutes of Health

NMDA receptor:

N-methyl-D-aspartate receptor

P-tau:

Phosphorylated tau

PD:

Parkinson’s disease

PDD:

Parkinson’s disease with dementia

PET:

Positron emission tomography

PNS:

Peripheral nervous system

PSP:

Progressive supranuclear palsy

RT-QuiC:

Real-time quaking-induced conversion assay

Simoa:

Single molecule array

SMA:

Spinal muscular atrophy

SNAP-25:

Synaptosomal-associated protein-25

SYT-1:

Synaptotagmin-1

TDP-43:

TAR DNA-binding protein 43

TREM2:

Triggering receptor expressed on myeloid cells 2

T-tau:

Total tau

VBI:

Vascular brain injury

YKL-40:

Chitinase-3-like protein 1

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Funding Supports and Acknowledgements

This was partly supported by Southwest University, Chongqing China to Prof. Sanjib Bhattacharyya (SWU Grant 5330500183). Lokesh Agarwal would like to acknowledge Prof. Shiga Takashi (University of Tsukuba) for his support for the visit to Bhattacharya lab (College of Pharmacy, Southwest University, China) and financial support from the self-inspired study travel grant (201730285, 2018) provided by the University of Tsukuba, Japan.

Data Availability Statement

Manuscript don’t contain any specific data since this is a review article, not an original research article. All the relevant figures are used with appropriate copyright permissions.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Chinese Traditional Medicine, Southwest University, Beibei, Chongqing, 400715, People’s Republic of China

    Nishit Pathak, Sunil Kumar Vimal, Cao Hongyi & Sanjib Bhattacharyya

  2. Amity University Jaipur, Rajasthan, Jaipur, Rajasthan, India

    Ishi Tandon

  3. Graduate School of Comprehensive Human Sciences, Kansei Behavioural and Brain Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan

    Lokesh Agrawal

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Contributions

NP wrote the substantial part of the manuscript whereas Parkinsonism part is written by IT. SKB and LA worked on making figure and chart for the manuscript. CH also have written a small part of the draft. SB has outlined the details, literature collection and conceptualized the total manuscript including editing and writing the introduction and conclusion. SB has also corresponded the manuscript.

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Correspondence to Sanjib Bhattacharyya.

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Pathak, N., Vimal, S.K., Tandon, I. et al. Neurodegenerative Disorders of Alzheimer, Parkinsonism, Amyotrophic Lateral Sclerosis and Multiple Sclerosis: An Early Diagnostic Approach for Precision Treatment . Metab Brain Dis 37, 67–104 (2022). https://doi.org/10.1007/s11011-021-00800-w

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