CNS Biomarkers, Modalities & Open Data Standards Glossary

Major lipid carrier in the central nervous system; the APOE ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease.

Highly sensitive fluid biomarker reflecting both cerebral amyloid-beta plaque burden and early tau tangle phosphorylation in Alzheimer's disease.

Presynaptic neuronal protein encoded by SNCA whose misfolding and fibrillar aggregation form Lewy bodies in Parkinson's disease and Lewy body dementia.

Nuclear RNA/DNA-binding protein whose cytoplasmic mislocalization, phosphorylation, and loss of nuclear splicing function drive >95% of ALS cases and ~50% of FTD.

Antioxidant enzyme gene; gain-of-toxicity mutations in SOD1 account for ~15-20% of familial ALS and are targeted by the approved antisense oligonucleotide Tofersen.

Hexanucleotide repeat expansion (GGGGCC) in C9orf72 is the most common genetic cause of both familial ALS and familial frontotemporal dementia (FTD).

Multidomain kinase/GTPase protein; activating mutations (such as G2019S) are the most common cause of autosomal-dominant Parkinson's disease.

Axonal cytoskeletal protein released into CSF and blood upon neuroaxonal injury; a cross-disease biomarker of neurodegeneration rate in ALS, MS, AD, and FTD.

Non-invasive neuroimaging modality measuring blood-oxygen-level-dependent (BOLD) hemodynamic signals to map brain network activity and functional connectivity.

Molecular neuroimaging technique using radiolabeled tracers to quantify in vivo protein pathology (amyloid plaques, tau tangles), glucose metabolism, or synaptic density.

MRI technique measuring anisotropic water diffusion along white matter tracts to quantify axonal integrity, demyelination, and structural connectomes.

High-temporal-resolution recording of postsynaptic cortical electrical potentials and neural oscillations (delta, theta, alpha, beta, gamma bands).

High-throughput transcriptomic profiling at individual cell or nucleus resolution, enabling identification of disease-associated microglia (DAM), astrocytes, and vulnerable neuronal subtypes.

Multimodal single-cell technique simultaneously capturing intrinsic electrophysiological properties, 3D axonal/dendritic morphology, and full-length transcriptome from the same neuron.

Subcellular-resolution spatial transcriptomics imaging hundreds to thousands of RNA species in intact brain tissue sections while preserving cytoarchitecture.

Community ISO-aligned standard for organizing and describing neuroimaging (MRI, fMRI, dMRI, PET) and neurophysiological (EEG, MEG, iEEG) datasets.

Unified data standard for cellular neurophysiology, packaging intracellular/extracellular recordings, optical physiology, and behavior into HDF5/Zarr files.

Standard Python/HDF5 container for single-cell and spatial omics, storing expression matrices (X) alongside cell annotations (obs), gene metadata (var), and embeddings (obsm).

Gold-standard 48-point clinical rating scale assessing bulbar, fine motor, gross motor, and respiratory function in ALS clinical trials.

Comprehensive four-part clinical rating scale quantifying non-motor experiences, activities of daily living, motor examination (Part III), and motor complications in Parkinson's disease.

Primary composite clinical endpoint in early Alzheimer's disease trials, summing 6 cognitive and functional domains (Memory, Orientation, Judgment, Community, Home, Personal Care; range 0–18).

Standard 0.0–10.0 ordinal clinical rating scale quantifying neurological disability across 8 functional systems and ambulation capacity in Multiple Sclerosis.

Irreversible accumulation of neurological disability occurring outside of clinical relapses, driven by diffuse smoldering neuroinflammation, chronic active lesions, and neuroaxonal loss in MS.

Chronic white matter MS lesions bordered by a dense rim of iron-laden, proinflammatory activated microglia/macrophages, visible on T2* phase MRI, SWI, and QSM.

MRI finding showing a small thin vein running centrally through a white matter hyperintense lesion on T2*-weighted / FLAIR* imaging, reflecting the perivenular pathology of Multiple Sclerosis.

Intermediate filament protein of astrocytes released into CSF and blood during reactive astrogliosis; tracks smoldering PIRA progression in MS and amyloid-induced astrocytic reactivity in Alzheimer's.

International consensus diagnostic framework integrating clinical attacks, MRI topography (Dissemination in Space/Time, optic nerve, CVS, PRLs), and CSF oligoclonal bands to diagnose MS.

Open-community clinical data standard that transforms heterogeneous hospital EHR and disease registry databases into a unified relational schema and standardized vocabulary for federated analytics.

Latent B-cell-tropic herpesvirus established as the leading causal environmental trigger of Multiple Sclerosis (~32-fold risk increase), driving CNS autoimmunity via EBNA1 molecular mimicry.

Oral small-molecule therapeutics crossing the blood-brain barrier to simultaneously inhibit B-cell receptor signaling and FcγR-mediated proinflammatory microglial activation in Multiple Sclerosis.

High-resolution near-infrared interferometric imaging of unmyelinated retinal axons (pRNFL) and ganglion cell neurons (GCIPL), serving as a non-invasive 'window into CNS neurodegeneration' in MS.