Neurological Differential Comprehensive Panel: ALS, MS & Alzheimer’s Molecular Research

The IM-NDCP is an RT-qPCR research panel designed for targeted analysis of 27 neurological disease-associated molecular biomarkers plus four reference genes.

Rather than relying on a single neurological marker, IM-Neuro31 organizes biomarkers into complementary disease-associated molecular signatures.

Priority I — Disease-Differentiation Core

ALS / TDP-43 Dysfunction

STMN2-CE, UNC13A-CE, HDGFL2-CE, POLDIP3-Splice

These four transcript-specific assays form the highest-priority ALS research component of the panel.

STMN2-CE

TDP-43-associated cryptic RNA-processing target involved in axonal maintenance, growth, and regeneration.

Loss of normal nuclear TDP-43 activity can result in abnormal STMN2 RNA processing and production of noncanonical transcripts.

Research significance:
TDP-43 dysfunction / motor-neuron and axonal biology.

UNC13A-CE

TDP-43-dependent cryptic-splicing target involved in synaptic vesicle release and neuronal communication.

Research significance:
TDP-43 loss-of-function, synaptic dysfunction, and ALS/FTD molecular biology.

HDGFL2-CE

TDP-43-dependent cryptic-exon target included as an additional functional indicator of altered RNA-splicing repression.

Research significance:
Functional characterization of TDP-43-associated RNA-processing abnormalities.

POLDIP3-Splice

Alternative-splicing assay designed to investigate changes associated with TDP-43 nuclear function.

Research significance:
Independent functional RNA-splicing readout of the TDP-43 pathway.

MS / Neuroimmune & Demyelinating Core

CXCL13, IL7R, HLA-DRA, CXCL9

CXCL13

B-cell-attracting chemokine associated with CNS immune activation and intrathecal inflammatory biology.

Research significance:
B-cell recruitment, neuroinflammation, and early inflammatory MS research.

IL7R

Interleukin-7 receptor involved in T-cell development, survival, and immune homeostasis and strongly associated with MS biology.

Research significance:
Adaptive immune regulation and MS susceptibility pathways.

HLA-DRA

Major histocompatibility complex class II component involved in antigen presentation and immune activation.

Research significance:
CNS immune activation and antigen-presentation pathways.

CXCL9

Interferon-responsive chemokine involved in activated immune-cell trafficking.

Research significance:
Inflammatory and T-cell-associated MS biology.

Alzheimer’s / Amyloid-Tau-Microglial Core

APP, BACE1, MAPT, TREM2

APP

Encodes amyloid precursor protein.

Research significance:
Amyloid precursor biology and Alzheimer-associated molecular pathways.

BACE1

Beta-secretase involved in amyloidogenic processing of APP.

Research significance:
Amyloid-processing pathway characterization.

MAPT

Encodes microtubule-associated protein tau.

Research significance:
Tau biology, neuronal cytoskeletal function, and neurodegeneration research.

TREM2

Microglial receptor involved in lipid sensing, phagocytosis, inflammatory responses, and responses to neuronal and amyloid-associated injury.

Research significance:
Microglial activation and Alzheimer-associated neuroimmune biology.

Priority II — Disease-Characterization Targets

ALS Characterization

TARDBP, KIF5A, SOD1, TBK1

TARDBP

Encodes TDP-43, a major RNA-binding protein regulating transcription, RNA processing, transport, stability, and splicing.

Research significance:
Central ALS/FTD RNA-processing pathway.

KIF5A

Kinesin-family motor protein involved in neuronal intracellular transport and long-range axonal trafficking.

Research significance:
Motor-neuron axonal transport and ALS-associated neuronal dysfunction.

SOD1

Antioxidant enzyme involved in protection against oxidative stress and one of the best-established genetically associated ALS pathways.

Research significance:
Oxidative-stress and genetically defined ALS research.

Note: Total SOD1 expression does not determine SOD1 mutation status.

TBK1

Protein kinase involved in autophagy, innate immune signaling, mitophagy, and interaction with proteins including OPTN.

Research significance:
ALS-associated proteostasis and cellular quality-control pathways.

Multiple Sclerosis Characterization

MOG, CHI3L1, IL12B, CXCR3

MOG

Myelin oligodendrocyte glycoprotein expressed in CNS myelin.

Research significance:
Oligodendrocyte and myelin-associated biology.

Note: MOG gene-expression analysis is distinct from anti-MOG antibody testing.

CHI3L1

Encodes chitinase-3-like protein 1, also known as YKL-40 at the protein level.

Research significance:
Glial activation, neuroinflammation, and progressive neurological-injury research.

IL12B

Encodes the p40 subunit shared by IL-12 and IL-23.

Research significance:
T-cell-associated inflammatory pathways relevant to autoimmune CNS disease.

CXCR3

Chemokine receptor associated with activated T-cell trafficking and inflammatory signaling.

Research significance:
Immune-cell recruitment and inflammatory MS biology.

Alzheimer’s Disease Characterization

APOE, PSEN1, CLU, ABCA7

APOE

Apolipoprotein involved in lipid transport, neuronal repair, amyloid biology, and microglial responses.

Research significance:
Major Alzheimer-associated lipid and neurodegenerative pathway.

Note: APOE gene-expression measurement does not determine APOE ε2/ε3/ε4 genotype.

PSEN1

Component of the γ-secretase complex involved in APP processing.

Research significance:
Amyloid-processing and familial Alzheimer-associated pathways.

CLU

Clusterin/apolipoprotein J is involved in lipid transport, protein homeostasis, complement regulation, and amyloid-associated biology.

Research significance:
Amyloid handling, lipid biology, and neuroinflammatory responses.

ABCA7

ATP-binding cassette transporter involved in lipid homeostasis, phagocytic biology, and Alzheimer-associated genetic pathways.

Research significance:
Microglial/lipid metabolism and amyloid-clearance research.

Priority III — Shared Neurodegeneration & Injury Markers

NEFL, NEFH, GFAP

These targets are intentionally classified as shared injury markers rather than disease-identification markers.

NEFL

Neurofilament light chain is a structural component of neuronal axons.

Research significance:
Axonal injury and neurodegeneration.

NEFH

Neurofilament heavy chain contributes to neuronal cytoskeletal organization and axonal structural integrity.

Research significance:
Axonal degeneration and motor-neuron injury.

GFAP

Glial fibrillary acidic protein is a major astrocytic intermediate-filament protein.

Research significance:
Astrocyte activation and CNS injury across multiple neurological conditions.

Reference Genes

TBP, RPLP0, HPRT1, PPIA

Multiple candidate reference genes are included to support normalization across experimental neurological research samples.

Panel Architecture

ALS — TDP-43 / Motor-Neuron Signature

Primary Differentiation Targets

STMN2-CE
UNC13A-CE
HDGFL2-CE
POLDIP3-Splice

Characterization Targets

TARDBP
KIF5A
SOD1
TBK1

Multiple Sclerosis — Neuroimmune / Demyelination Signature

Primary Differentiation Targets

CXCL13
IL7R
HLA-DRA
CXCL9

Characterization Targets

MOG
CHI3L1
IL12B
CXCR3

Alzheimer’s Disease — Amyloid / Tau / Microglial Signature

Primary Differentiation Targets

APP
BACE1
MAPT
TREM2

Characterization Targets

APOE
PSEN1
CLU
ABCA7

Shared Neurodegeneration

NEFL
NEFH
GFAP

Reference / Normalization

TBP
RPLP0
HPRT1
PPIA

Complete IM-Neuro31 Target List

ALS — 8 Assays

STMN2-CE, UNC13A-CE, HDGFL2-CE, POLDIP3-Splice, TARDBP, KIF5A, SOD1, TBK1

Multiple Sclerosis — 8 Targets

CXCL13, IL7R, HLA-DRA, CXCL9, MOG, CHI3L1, IL12B, CXCR3

Alzheimer’s Disease — 8 Targets

APP, BACE1, MAPT, TREM2, APOE, PSEN1, CLU, ABCA7

Shared Neurodegeneration — 3 Targets

NEFL, NEFH, GFAP

Reference Genes — 4 Targets

TBP, RPLP0, HPRT1, PPIA

TOTAL: 31 ASSAYS

27 neurological research biomarkers + 4 reference genes

Suggested Research Interpretation Framework

The IM-Neuro31 panel is designed to support investigation of coordinated molecular patterns rather than interpretation of individual biomarkers in isolation.

ALS TDP-43 Dysfunction Signature

STMN2-CE + UNC13A-CE + HDGFL2-CE + POLDIP3-Splice

Designed to investigate coordinated loss of normal TDP-43-dependent RNA-processing activity.

ALS Characterization Signature

TARDBP + KIF5A + SOD1 + TBK1

Designed to investigate RNA metabolism, axonal transport, oxidative-stress, and proteostasis pathways associated with ALS biology.

MS Neuroimmune Signature

CXCL13 + IL7R + HLA-DRA + CXCL9

Designed to investigate B-cell/T-cell recruitment, antigen presentation, and CNS inflammatory activity.

MS Demyelination/Inflammatory Signature

MOG + CHI3L1 + IL12B + CXCR3

Designed to investigate myelin-associated biology, glial activation, inflammatory signaling, and immune-cell trafficking.

Alzheimer’s Amyloid/Tau Signature

APP + BACE1 + MAPT + PSEN1

Designed to investigate amyloid-processing and tau-associated pathways.

Alzheimer’s Microglial/Lipid Signature

TREM2 + APOE + CLU + ABCA7

Designed to investigate microglial responses, lipid metabolism, amyloid handling, and genetically associated AD pathways.

Neurodegeneration Index

NEFL + NEFH + GFAP

Designed to investigate shared neuronal, axonal, and astroglial injury.