# Decoding the Metabolic Signatures of Neurodegeneration Diseases: Advances in Mass Spectrometry-Based Metabolomics

**Authors:** Md Abdul Hakim, Li Li

PMC · DOI: 10.3390/metabo16030206 · 2026-03-20

## TL;DR

This review discusses how mass spectrometry-based metabolomics is helping to uncover metabolic changes in neurodegenerative diseases.

## Contribution

The paper highlights recent methodological and bioinformatics advancements in metabolomics for studying neurodegeneration.

## Key findings

- Mass spectrometry improvements allow broader detection and accurate identification of metabolites.
- Signature metabolites and key pathways linked to major neurodegenerative diseases are summarized.
- Current challenges and future translational directions in metabolomics are explored.

## Abstract

The dysregulation of multiple metabolic pathways is a potential contributor to the development of neurodegenerative diseases. Understanding early-stage metabolic alterations is crucial for identifying targets associated with disease development and progression. Recent advances in mass spectrometry-based metabolomics now allow investigators to conduct a comprehensive analysis of small-molecule metabolites in complex biological systems, providing valuable insights regarding the biochemical mechanisms underlying neurodegeneration. This review presents the latest advances in mass spectrometry-based metabolomic approaches and their applications in studying neurodegenerative diseases. We discuss methodology improvements in metabolomics, including sample preparation, chromatography separations, ionization, and fragmentation. These improvements enable broader detection and more accurate identification of metabolites. We also review developments in bioinformatics tools for large-scale data processing, structural annotation, and pathway analysis. Furthermore, the signature metabolites associated with major neurodegenerative diseases and the key metabolic pathways involved are summarized. Finally, we address current analytical and biological challenges in mass spectrometry-based metabolomics while exploring its future directions in translational research.

## Full-text entities

- **Genes:** CYP46A1 (cytochrome P450 family 46 subfamily A member 1) [NCBI Gene 10858] {aka CP46, CYP46}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, DHCR24 (24-dehydrocholesterol reductase) [NCBI Gene 1718] {aka DCE, Nbla03646, SELADIN1, seladin-1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, TARDBP (TAR DNA binding protein) [NCBI Gene 23435] {aka ALS10, TDP-43}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, FSIP1 (fibrous sheath interacting protein 1) [NCBI Gene 161835] {aka HSD10}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, LDLR (low density lipoprotein receptor) [NCBI Gene 3949] {aka LDLCQ2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** type 2 diabetes (MESH:D003924), stroke (MESH:D020521), synaptic injury (MESH:D012183), Tauopathy (MESH:D024801), injury to (MESH:D014947), insulin resistance (MESH:D007333), MCI (MESH:D060825), Mitochondrial Dysfunction (MESH:D028361), diabetes (MESH:D003920), neurological diseases (MESH:D020271), HD (MESH:D006816), Neurodegeneration Diseases (MESH:D019636), type III diabetes (MESH:D003922), neurotoxic (MESH:D020258), cognitive decline (MESH:D003072), Alzheimer's and Parkinson's disease (MESH:D010300), neuroinflammation (MESH:D000090862), FTD (MESH:D057180), impaired glucose metabolism (MESH:D044882), multiple sclerosis (MESH:D009103), cancer (MESH:D009369), MS (MESH:C536030), mitochondrial fragmentation (MESH:D012892), -related diseases (MESH:D000077733), metabolic dysfunction (MESH:D008659), dementia (MESH:D003704), ALS (MESH:D000690), vascular dementia (MESH:D015140), inflammation (MESH:D007249), fatty liver (MESH:D005234), breast cancer (MESH:D001943), neurological dysfunction (MESH:D009461), dementia with Lewy bodies (MESH:D020961), poisoning (MESH:D011041), clear cell renal cell carcinoma (MESH:D002292), phenylketonuria (MESH:D010661), AD (MESH:D000544)
- **Chemicals:** lactate (MESH:D019344), eicosatrienoic acid (MESH:C094477), beta-alanine (MESH:D015091), D-arabitol (MESH:C014999), fatty acids (MESH:D005227), carbon (MESH:D002244), polyvinyl alcohol (MESH:D011142), oxygen (MESH:D010100), 9-aminoacridine (MESH:D000585), threonine (MESH:D013912), ganglioside GM3 (MESH:D005679), 6-octadecenoic acid (MESH:C008820), Glutamine (MESH:D005973), branched-chain amino acids (MESH:D000597), N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MESH:C086665), carnitine (MESH:D002331), 13C (MESH:C000615229), trifluoroacetic acid (MESH:D014269), alanine (MESH:D000409), purine (MESH:C030985), carboxylic acids (MESH:D002264), citrate (MESH:D019343), sodium deoxycholate (MESH:D003840), 2-nitrophenylpentyl ether (-), linoleate (MESH:D019787), Cholesterol (MESH:D002784), 2-nonanone (MESH:C026636), gamma-aminobutyric acid (MESH:D005680), creatine (MESH:D003401), allantoin (MESH:D000481), polychlorinated biphenyls (MESH:D011078), phenylalanine (MESH:D010649), serine (MESH:D012694), 4,5-dihydroorotic acid (MESH:C004768), succinyl-CoA (MESH:C012046), 24(S)-hydroxycholesterol (MESH:C044563), malathion (MESH:D008294), TCA (MESH:D014238), desmosterol (MESH:D003897), fumarate (MESH:D005650), fat (MESH:D005223), D-galactose (MESH:D005690), 27-OHC (MESH:C076996), oxysterol (MESH:D000072376), Lipid (MESH:D008055), methyl tert-butyl ether (MESH:C043243), spermidine (MESH:D013095), tryptophan (MESH:D014364), 2,5-dihydroxybenzoic acid (MESH:C010925), tauroursodeoxycholic acid (MESH:C031655), inositol (MESH:D007294), maltose (MESH:D008320), 1,25-dihydroxyvitamin D3 (MESH:D002117), arginine (MESH:D001120), anthranilic acid (MESH:C031385), sphingomyelin (MESH:D013109), uridine diphosphate (MESH:D014530), propyl gallate (MESH:D011435), sphingolipid (MESH:D013107), methanol (MESH:D000432)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Sus scrofa (pig, species) [taxon 9823], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13027704/full.md

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Source: https://tomesphere.com/paper/PMC13027704