Proteomic Analysis of Alzheimer’s Disease Brain

Proteomic analysis of Alzheimer’s disease (AD) brain encompasses large-scale measurement of protein identities, abundances and modifications to elucidate molecular mechanisms underpinning neurodegeneration. By applying advanced mass spectrometry workflows to post-mortem tissue and biofluids such as cerebrospinal fluid (CSF), researchers have charted the temporal and spatial evolution of protein networks associated with hallmark pathologies—amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs)—as well as synaptic dysfunction, metabolic disturbance and neuroinflammation. Co-expression network analysis further organises proteins into functional modules, revealing stage-specific changes in mitochondrial pathways, immune response and protein homeostasis. Integration of multi-region brain maps with CSF proteomes offers routes to precision biomarkers and therapeutic targets, while comparative studies across populations and in vitro models refine our understanding of genetic, racial and metabolic influences on the proteomic landscape of AD.

Research from Nature Portfolio

Recent studies have employed longitudinal CSF proteomics in autosomal dominant AD to characterise protein trajectories over decades, revealing early elevations in plaque-associated proteins followed by synaptic, metabolic and inflammatory alterations long before clinical onset. In parallel, in vivo proteomic profiling combined with PET ligands for Aβ and tau has identified distinct sets of differentially abundant proteins linked to glial immune response and neuronal energy metabolism, distinguishing AD from other neurodegenerative proteomes and uncovering co-expression modules with opposing dynamics along the disease continuum. A comprehensive meta-analysis of human brain proteomic datasets has generated a searchable atlas of consistently altered proteins across brain regions and disease stages, highlighting early synaptic and vesicular changes and late-stage mitochondrial deficits, thus providing a foundational resource for biomarker discovery and mechanistic studies.

Proteomic Analysis of Alzheimer’s Disease Brain publication trend

The graph below shows the total number of articles in proteomic analysis of alzheimer’s disease brain across all publications each year (not limited to Nature Index journals).

Technical terms

Proteomics: The large-scale study of the full complement of proteins, their quantities and modifications in a biological sample.

Mass spectrometry: An analytical technique used to measure the mass-to-charge ratio of ions, enabling identification and quantification of proteins and peptides.

Cerebrospinal fluid (CSF): A clear biofluid surrounding the brain and spinal cord, commonly analysed for biomarkers of neurological disease.

Amyloid-β (Aβ) plaques: Extracellular aggregates of Aβ peptides, one of the pathological hallmarks of Alzheimer’s disease.

Neurofibrillary tangles (NFTs): Intracellular accumulations of hyperphosphorylated tau protein, characteristic of Alzheimer’s pathology.

References

1. Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease. Nature Medicine (2023).
2. Proteomic changes in Alzheimer’s disease associated with progressive Aβ plaque and tau tangle pathologies. Nature Neuroscience (2024).
3. Quantitative proteomics of cerebrospinal fluid from African Americans and Caucasians reveals shared and divergent changes in Alzheimer’s disease. Molecular Neurodegeneration (2023).
4. Compilation of reported protein changes in the brain in Alzheimer’s disease. Nature Communications (2023).
5. Metabolic Bypass Rescues Aberrant S‐nitrosylation‐Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons. Advanced Science (2024).