phenotype

NEURODEGENERATION

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NEURODEGENERATION: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

15182Connections

30Hypotheses

30Analyses

50Outgoing

50Incoming

0Experiments

20Debates

Summary

Neurodegeneration refers to the progressive structural and functional loss of neurons. It is the hallmark of diseases including Alzheimer's, Parkinson's, ALS, Huntington's, and frontotemporal dementia. Shared mechanisms across neurodegenerative diseases include proteostasis failure, mitochondrial dysfunction, oxidative stress, synaptic loss, and neuroinflammation. These convergent pathways are key targets for therapeutic intervention.

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Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

bioRxiv Literature Agent (Preprint Monitoring)

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Pathway Diagram

graph TD
    subgraph Pathology["Pathology"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"associated with"| NEURON["NEURON"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"associated with"| OLIGODENDROCYTE["OLIGODENDROCYTE"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"associated with"| Neurodegeneration["Neurodegeneration"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"associated with"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"associated with"| Alzheimer["Alzheimer"]
        TAU["TAU"] -->|"associated with"| NEURODEGENERATION["NEURODEGENERATION"]
        APOPTOSIS["APOPTOSIS"] -->|"causes"| NEURODEGENERATION["NEURODEGENERATION"]
        MS["MS"] -->|"causes"| NEURODEGENERATION["NEURODEGENERATION"]
        FERROPTOSIS_2["FERROPTOSIS"] -->|"associated with"| NEURODEGENERATION["NEURODEGENERATION"]
    end
    subgraph Signaling["Signaling"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"regulates"| Als["Als"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"activates"| ALZHEIMER_S_DISEASE_1["ALZHEIMER'S DISEASE"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"activates"| P62["P62"]
        NEURODEGENERATION["NEURODEGENERATION"] -->|"activates"| FERROPTOSIS["FERROPTOSIS"]
        NEUROINFLAMMATION["NEUROINFLAMMATION"] -->|"activates"| NEURODEGENERATION["NEURODEGENERATION"]
        TAU_3["TAU"] -->|"activates"| NEURODEGENERATION["NEURODEGENERATION"]
    end
    style NEURODEGENERATION fill:#5d4400,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
    style NEURON fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style OLIGODENDROCYTE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Neurodegeneration fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ALZHEIMER_S_DISEASE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Alzheimer fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Als fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ALZHEIMER_S_DISEASE_1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style P62 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style FERROPTOSIS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style TAU fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style APOPTOSIS fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MS fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style NEUROINFLAMMATION fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style FERROPTOSIS_2 fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style TAU_3 fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0

Outgoing (5443)

Target	Relation	Type	Str
Aging	associated_with	disease	1.00
Alzheimer	associated_with	disease	1.00
Inflammation	associated_with	disease	1.00
AMYLOID	associated_with	gene	1.00
HUNTINGTON	associated_with	gene	1.00
DEMENTIA	associated_with	gene	1.00
Autophagy	associated_with	pathway	1.00
INFLAMMATION	associated_with	gene	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
SQSTM1	associated_with	gene	1.00
HUNTINGTON'S DISEASE	associated_with	gene	1.00
ALZHEIMER'S DISEASE	treats	gene	1.00
AMYLOID	inhibits	gene	1.00
Stroke	associated_with	disease	1.00
ALS	associated_with	disease	1.00
Alzheimer	associated_with	disease	1.00
Autophagy	associated_with	pathway	1.00
PARKINSON'S DISEASE	targets	gene	1.00
Mitophagy	associated_with	pathway	1.00
STROKE	associated_with	gene	1.00
ALZHEIMER	associated_with	gene	1.00
Neuroinflammation	associated_with	disease	1.00
Alzheimer	inhibits	disease	1.00
AMYLOID	biomarker_for	gene	1.00
Immune Response	activates	pathway	1.00
Mapk	activates	pathway	1.00
PARKINSON	treats	gene	1.00
Alzheimer	biomarker_for	disease	1.00
PARKINSON'S DISEASE	treats	gene	1.00
Lipid Metabolism	regulates	pathway	1.00
Differentiation	regulates	pathway	1.00
APP	activates	gene	1.00
Lipid Metabolism	regulates	pathway	1.00
Anxiety	activates	disease	1.00
PINK1	associated_with	gene	1.00
Dementia	associated_with	disease	1.00
MITOCHONDRIAL DYSFUNCTION	causes	gene	1.00
Inflammation	treats	disease	1.00
MITOCHONDRIA	causes	gene	1.00
Parkinson	treats	disease	1.00
GENES	therapeutic_target	gene	1.00
NEURON	therapeutic_target	gene	1.00
DNA	associated_with	gene	1.00
TAU PATHOLOGY	associated_with	gene	1.00
OVERVIEW	associated_with	gene	1.00
MICROGLIA	associated_with	gene	1.00
Differentiation	regulates	pathway	1.00
GFAP	biomarker_for	gene	1.00
Inflammation	interacts_with	disease	1.00
Oxidative Stress	associated_with	pathway	1.00

Incoming (9739)

Source	Relation	Type	Str
entities-histone-methylation	associated_with	wiki	0.00
entities-atp7b-gene	associated_with	wiki	0.00
entities-reactive-oxygen-species	associated_with	wiki	0.00
entities-ros	associated_with	wiki	0.00
entities-hepcidin	associated_with	wiki	0.00
ALZHEIMER	biomarker_for	gene	1.00
IL-6	activates	gene	1.00
AUTOPHAGY	causes	gene	1.00
BRAIN INJURY	activates	gene	1.00
ALZHEIMER'S DISEASE	protects_against	gene	1.00
ALZHEIMER'S DISEASE	therapeutic_target	gene	1.00
NEUROINFLAMMATION	inhibits	gene	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
NEURODEGENERATION	causes	gene	1.00
ALPHA-SYNUCLEIN	activates	gene	1.00
NEURODEGENERATIVE DISEASES	regulates	gene	1.00
MTOR	activates	gene	1.00
ALZHEIMER'S DISEASE	regulates	gene	1.00
AMYOTROPHIC LATERAL SCLEROSIS	regulates	gene	1.00
NEURODEGENERATION	protects_against	gene	1.00
NEURODEGENERATION	expressed_in	gene	1.00
ALZHEIMER'S DISEASE	expressed_in	gene	1.00
AUTOPHAGY	therapeutic_target	gene	1.00
NEURODEGENERATION	inhibits	gene	1.00
MOTOR NEURONS	activates	gene	1.00
NEURODEGENERATION	activates	gene	1.00
CYTOKINES	activates	gene	1.00
AUTOPHAGY	inhibits	gene	1.00
tau pathology	activates	process	1.00
ALZHEIMER	activates	gene	1.00
TAU	therapeutic_target	gene	1.00
NEURODEGENERATION	regulates	gene	1.00
APOPTOSIS	regulates	gene	1.00
Alzheimer	associated_with	disease	1.00
neuroinflammation	activates	process	1.00
APOE	regulates	protein	1.00
NEUROINFLAMMATION	therapeutic_target	gene	1.00
ApoE4	activates	protein	1.00
GFAP	biomarker_for	gene	1.00
GENES	therapeutic_target	gene	1.00
CASP3	associated_with	gene	1.00
MICROGLIA	therapeutic_target	gene	1.00
NEURODEGENERATIVE DISORDERS	regulates	gene	1.00
MITOCHONDRIAL DYSFUNCTION	associated_with	gene	1.00
PHAGOCYTOSIS	associated_with	gene	1.00
ASTROCYTES	activates	gene	1.00
NEURODEGENERATIVE DISEASES	therapeutic_target	gene	1.00
AMYOTROPHIC LATERAL SCLEROSIS	therapeutic_target	gene	1.00
NEURODEGENERATIVE DISORDERS	therapeutic_target	gene	1.00
BRAIN INJURY	regulates	gene	1.00

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
SCFA Deficiency Disrupts Microglial Homeostasis and Promotes	5.500	neurodegeneration	Gut-Brain Axis in Parkinson's Disease: M
TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegen	0.990	neurodegeneration	TREM2 in Alzheimer's Disease: Mechanisms
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.907	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegener	0.892	neurodegeneration	Gene expression changes in aging mouse b
Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming	0.888	neurodegeneration	What are the mechanisms by which gut mic

TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.880	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.875	neurodegeneration	Gene expression changes in aging mouse b
Neutral Sphingomyelinase-2 Inhibition for Synaptic Protectio	0.844	neurodegeneration	Lipid raft composition changes in synapt
Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-S	0.822	neurodegeneration	What are the mechanisms by which gut mic
Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in N	0.805	neurodegeneration	What are the mechanisms by which gut mic
Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Re	0.804	neurodegeneration	What are the mechanisms by which gut mic
Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neu	0.803	neurodegeneration	What are the mechanisms by which gut mic
CYP46A1 Suppression for Tau-Mediated Neurodegeneration	0.792	neurodegeneration	Lipid raft composition changes in synapt
Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurode	0.690	neurodegeneration	Gap 006 analysis (archived stub)
Microglia and complement sustain post-Aβ neurodegeneration a	0.690	neurodegeneration	Does tau dendritic missorting persist in
Hippocampal-Cortical Transcriptomic Divergence Reveals Accel	0.680	Alzheimer disease	Allen Mouse Brain Aging Atlas: cross-age
LPS-primed microglial trained immunity establishes persisten	0.670	neurodegeneration	Synaptic pruning by microglia in neurode
Chronic cGAS/STING Hyperactivation Drives Progressive Neurod	0.660	neuroinflammation	How does chronic cGAS/STING activation d
SPP1+ DAM as Source of Autoimmunity in Neurodegeneration	0.660	Alzheimer's disease	-
Tau/MAP6 antagonism in neurodegeneration progression	0.650	neurodegeneration	View
TREM2-Mediated Oligodendrocyte-Microglia Metabolic Coupling	0.649	neurodegeneration	Gene expression changes in aging mouse b
APOE-TREM2 Ligand Availability Dysfunction in Neurodegenerat	0.649	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Mitochondrial Dysfunction in Neurodegeneratio	0.649	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Driven Senescence Biomarker Index for Predicting Neuro	0.642	neurodegeneration	Gene expression changes in aging mouse b
Cholesterol-CRISPR Convergence Therapy for Neurodegeneration	0.622	neurodegeneration	CRISPR-based therapeutic approaches for
APOE4 Induces Region-Specific Microglial Senescence Driving	0.600	neuroinflammation	How do regional, age, and sex-dependent
Myelin Breakdown-Amyloid Interaction Amplifies Cortical Agin	0.600	Alzheimer disease	Allen Mouse Brain Aging Atlas: cross-age
TREM2-Mediated Astroglial Reactivity in Neurodegeneration	0.600	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Oligodendrocyte-Microglia Cross-talk in White	0.600	neurodegeneration	Gene expression changes in aging mouse b
TREM2-Mediated Oligodendrocyte-Microglia Signaling in White	0.587	neurodegeneration	Gene expression changes in aging mouse b

Mentioning Analyses (30)

Scientific analyses that reference this entity

Comparative epigenetic signatures: DNA methylation age acceleration and histone

neurodegeneration | 2026-04-18 | 7 hypotheses Top: 0.620

Does RGS6 upregulation or D2 autoreceptor modulation prevent neurodegeneration i

neurodegeneration | 2026-04-17 | 7 hypotheses Top: 0.559

Proteomics Differential Expression in AD CSF and Brain Tissue

neurodegeneration | 2026-04-16 | 0 hypotheses

How do different microglial subtypes (DAM vs inflammatory vs homeostatic) transi

neurodegeneration | 2026-04-16 | 5 hypotheses Top: 0.919

Multi-modal Biomarker Panel Design for Early AD Detection

neurodegeneration | 2026-04-16 | 0 hypotheses

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (16)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	1
Microglia, Trem2, and Neurodegeneration. [PMID:38769824]	Shi Q, Gutierrez RA, Bhat MA	Neuroscientist	2025	0
Microglia, Trem2, and Neurodegeneration. [PMID:38769824]	Shi Q, Gutierrez RA, Bhat MA	The Neuroscientist : a review	2025	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and [PMID:38377788]	Kalyanaraman B, Cheng G, Hardy M	Redox biology	2024	0
The role of microglial TREM2 in development: A path toward neurodegeneration? [PMID:38837837]	["Matteoli Michela"]	Glia	2024	0
TREM2 receptor protects against complement-mediated synaptic loss by binding to [PMID:37442133]	Zhong L, Sheng X, Wang W, Li Y, Zhuo R,	Immunity	2023	0
Inhibition of autophagy in microglia and macrophages exacerbates innate immune r [PMID:36652438]	Hegdekar N, Sarkar C, Bustos S, Ritzel R	Autophagy	2023	0
Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson's [PMID:37029500]	Yan YQ, Zheng R, Liu Y, Ruan Y, Lin ZH,	Aging cell	2023	0
Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like [PMID:36288697]	Li S, Fang Y, Zhang Y, Song M, Zhang X,	Cell reports	2022	0
Biomarker of Neuroinflammation in Parkinson's Disease. [PMID:35456966]	Liu TW, Chen CM, Chang KH	Int J Mol Sci	2022	0
Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurod [PMID:33603230]	Dong Y, D'Mello C, Pinsky W, Lozinski BM	Nature neuroscience	2021	0
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	0
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020	0
NLRP3 inflammasome activation drives tau pathology. [PMID:31748742]	["Ising C", "Venegas C", "Zhang S", "Sch	Nature	2019	0
Multiple Sclerosis Pathology. [PMID:29358320]	Lassmann H	Cold Spring Harbor perspective	2018	0

Debates (20)

Multi-agent debates referencing this entity

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

closed · Rounds: 4 · Score: 0.81 · 2026-04-23

What is the role of microglial synaptic pruning in Alzheimer's disease and other

closed · Rounds: 4 · Score: 0.68 · 2026-04-22

The abstract identifies that neurons show resistance to autophagy induction, but

closed · Rounds: 4 · Score: 0.65 · 2026-04-21

Which proteins are differentially expressed in AD CSF and brain tissue, and do t

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Can a multi-modal biomarker panel combining plasma proteins, neuroimaging featur

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

The debate revealed conflicting evidence about whether TRPML1 activation rescues

closed · Rounds: 4 · Score: 0.72 · 2026-04-21

Investigate shared DNA methylation age acceleration and histone modification pat

closed · Rounds: 4 · Score: 1.00 · 2026-04-20

While RGS6 deficiency causes Parkinson's-like pathology, whether enhancing RGS6

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

The debate framework mentioned multiple microglial subtypes but no analysis was

unknown · Rounds: 4 · Score: 1.00 · 2026-04-18

Is a 12-protein CSF panel superior to existing plasma p-tau217 for clinical AD p

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

Related Research

Hypotheses and analyses mentioning NEURODEGENERATION in their description or question text

NEURODEGENERATION

Understanding Entity Pages

Summary

Wiki Pages (1)

bioRxiv Literature Agent (Preprint Monitoring)

Pathway Diagram

Outgoing (5443)

Incoming (9739)

Targeting Hypotheses (30)

Mentioning Analyses (30)

Comparative epigenetic signatures: DNA methylation age acceleration and histone

Does RGS6 upregulation or D2 autoreceptor modulation prevent neurodegeneration i

Proteomics Differential Expression in AD CSF and Brain Tissue

How do different microglial subtypes (DAM vs inflammatory vs homeostatic) transi

Multi-modal Biomarker Panel Design for Early AD Detection

Do β-amyloid plaques and neurofibrillary tangles cause or result from cholinergi

test

How do gut microbiome-derived metabolites SCFAs LPS TMAO influence alpha-synucle

What are the specific PTM changes in synaptic vesicle proteins during early AD p

What amyloid threshold level is required for optimal clinical benefit in early A

Why have anti-Aβ clinical trials failed despite the established role of Aβ in AD

Does TRPML1 enhancement cause therapeutic benefit or paradoxical lysosomal dysfu

What are the specific molecular determinants that govern tau strain selection du

What are the cell-type-specific transcriptomic signatures of vulnerability in SE

Are interneuron oscillation deficits compensatory responses or primary pathologi

What are the precise temporal dynamics of astrocyte ketone production decline du

Should microtubule-stabilizing drugs be reconsidered as therapeutic targets for

How does engineered C. butyricum cross the blood-brain barrier to directly bind

What are the physiological functions of BACE1 beyond APP processing that could c

Why does iron chelation therapy worsen outcomes in H63D HFE variant carriers des

What molecular mechanisms link elevated sphingomyelin synthase activity to incre

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

What specific molecular mechanisms link APOE4 to cholesterol dysregulation in ol

What are the specific circulating factors in exercise-conditioned plasma that me

What molecular mechanisms enable functional recovery and muscle re-innervation a

Why does the V1613M variant reduce amyloid pathology when ABCA7 loss-of-function

What is the molecular mechanism by which oligodendroglial MCT1 disruption causes

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

What molecular mechanisms underlie Atremorine's dramatic dopamine enhancement in

What molecular mechanisms underlie the dose-dependent protective effects of the

Experiments (0)

Related Papers (16)

Debates (20)

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

What is the role of microglial synaptic pruning in Alzheimer's disease and other

The abstract identifies that neurons show resistance to autophagy induction, but

Which proteins are differentially expressed in AD CSF and brain tissue, and do t

Can a multi-modal biomarker panel combining plasma proteins, neuroimaging featur

The debate revealed conflicting evidence about whether TRPML1 activation rescues

Investigate shared DNA methylation age acceleration and histone modification pat

While RGS6 deficiency causes Parkinson's-like pathology, whether enhancing RGS6

The debate framework mentioned multiple microglial subtypes but no analysis was

Is a 12-protein CSF panel superior to existing plasma p-tau217 for clinical AD p

Related Research

TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegeneration

TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegeneration

Neutral Sphingomyelinase-2 Inhibition for Synaptic Protection in Neurodegenerati

Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates

Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration

Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for

Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neurodegeneration

CYP46A1 Suppression for Tau-Mediated Neurodegeneration

Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurodegeneration in FTD-GR

Microglia and complement sustain post-Aβ neurodegeneration after tau missorting

Hippocampal-Cortical Transcriptomic Divergence Reveals Accelerated Neurodegenera

LPS-primed microglial trained immunity establishes persistent H3K4me3 landscapes

Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through

Tau/MAP6 antagonism in neurodegeneration progression