Encephalopathy Connectomic Collapse Atlas (ECCA-NDEG) | Neurodegenerative Encephalopathy Biomarker Panel

SCF-ECCA-NDEG-BIO-0009

Neurodegenerative Encephalopathy Biomarker Panel

Progressive Neurodegenerative Connectomic Collapse Validation System

FDA-Aligned Endpoint Framework for Precision Acupuncture Planning

Encephalopathy Connectomic Collapse Atlas (ECCA-NDEG)

I. PURPOSE

The SCF Neurodegenerative Encephalopathy Biomarker Panel is designed to:

Establish neurodegenerative encephalopathy diagnostic support
Quantify progressive connectomic collapse
Differentiate major neurodegenerative subtypes
Predict cognitive, autonomic, motor, and behavioral decline
Enable precision acupuncture treatment planning
Monitor disease progression longitudinally
Support FDA-aligned translational endpoint development
Forecast resilience versus degeneration trajectories

II. SCF ETIOPATHOGENIC CORE

Neurodegenerative encephalopathy is characterized by:

Progressive proteinopathy
Synaptic degeneration
Neuroimmune activation
Mitochondrial dysfunction
Glymphatic failure
White matter network deterioration
Neurovascular aging
Limbic-connectomic fragmentation
Progressive cognitive collapse

Principal Disease Classes

Disease Group	Dominant Proteinopathy
Alzheimer’s Disease	Aβ + Tau
Lewy Body Disease	α-Synuclein
Parkinsonian Dementia	α-Synuclein
Frontotemporal Dementia	Tau / TDP-43
ALS-FTD Spectrum	TDP-43
Prion Disorders	PrPSc
Mixed Dementia	Multi-proteinopathy

III. PROTEINOPATHY PANEL

Tier 1 Primary Disease Driver Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
Plasma pTau217	Simoa	Reference	Elevated	High	Very High
Plasma pTau181	Simoa	Reference	Elevated	High	Very High
Aβ42/40 Ratio	Mass Spectrometry	Normal	Mild Reduction	Moderate Reduction	Severe Reduction
α-Synuclein	RT-QuIC / ELISA	Normal	Elevated	High	Very High
TDP-43	ELISA	Normal	Elevated	High	Very High
PrPSc	RT-QuIC	Negative	Positive	High	Very High

Endpoint

Proteinopathy Burden Index (PBI)

IV. SYNAPTIC DEGENERATION PANEL

Tier 2 Synaptic Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Neurogranin	ELISA	Reference	Elevated	High	Very High
SNAP-25	ELISA	Reference	Elevated	High	Very High
Synaptotagmin	ELISA	Reference	Elevated	High	Very High
GAP-43	ELISA	Reference	Elevated	High	Very High

Endpoint

Synaptic Failure Index (SFI)

V. NEUROAXONAL DEGENERATION PANEL

Tier 3 Axonal Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
NfL	Simoa	<10 pg/mL	10–20	20–50	>50
Total Tau	Simoa	<2 pg/mL	2–4	4–8	>8
UCH-L1	ELISA	<100 pg/mL	100–200	200–400	>400
NSE	CLIA	<12 ng/mL	12–18	18–25	>25

Endpoint

Neurodegenerative Injury Index (NDII)

VI. GLIAL ACTIVATION PANEL

Tier 4 Neuroimmune Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
GFAP	Simoa	<120 pg/mL	120–250	250–500	>500
YKL-40	ELISA	<60 ng/mL	60–100	100–150	>150
sTREM2	ELISA	Normal	Elevated	High	Very High
MCP-1	Multiplex	Reference	Elevated	High	Very High
CCL5	Multiplex	Reference	Elevated	High	Very High

Endpoint

Neuroimmune Degeneration Score (NDS)

VII. GLYMPHATIC FAILURE PANEL

Tier 5 Clearance Dysfunction Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
AQP4 Autoantibodies	ELISA	Negative	Borderline	Positive	High
CSF Aβ Clearance Rate	Dynamic CSF Study	Normal	Reduced	Markedly Reduced	Severe Failure
Perivascular Space Burden	MRI	Normal	Mild	Moderate	Severe
Sleep Efficiency	PSG	>85%	75–85%	60–75%	<60%

Endpoint

Glymphatic Collapse Index (GCI)

VIII. BBB INTEGRITY PANEL

Tier 6 Neurovascular Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Albumin Quotient	CSF/Serum	<6.5	6.5–8	8–12	>12
MMP-9	ELISA	<150 ng/mL	150–250	250–400	>400
VEGF	ELISA	Normal	Elevated	High	Very High
S100B	<0.1 ng/mL	0.1–0.2	0.2–0.5	>0.5	Severe

Endpoint

Neurovascular Degeneration Index (NDVI)

IX. MITOCHONDRIAL FAILURE PANEL

Tier 7 Bioenergetic Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Lactate/Pyruvate Ratio	LC-MS/MS	<20	20–30	30–40	>40
ATP Production	Seahorse	Normal	↓10%	↓25%	↓50%
CoQ10	LC-MS/MS	Normal	Mild Deficit	Moderate	Severe
cf-mtDNA	qPCR	Low	Elevated	High	Very High

Endpoint

Bioenergetic Degeneration Index (BDI)

X. CONNECTOMIC COLLAPSE PANEL

Tier 8 Network Fragmentation Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
EEG Delta Excess	qEEG	Normal	+20%	+50%	+100%
Alpha Connectivity	qEEG	Normal	↓10%	↓25%	↓50%
rs-fMRI Connectivity	MRI	Normal	↓10%	↓25%	↓50%
DTI Fractional Anisotropy	MRI-DTI	Normal	↓5%	↓10%	↓20%
Hippocampal Volume	MRI	Normal	↓5%	↓15%	↓30%

Endpoint

Connectomic Degeneration Index (CDI)

XI. AUTONOMIC DEGENERATION PANEL

Tier 9 Brainstem-Limbic Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
HRV SDNN	>100 ms	80–100	50–80	<50	Severe
RMSSD	>30 ms	20–30	10–20	<10	Severe
LF/HF Ratio	1–2	2–3	3–5	>5	Severe
Orthostatic Dysfunction	None	Mild	Moderate	Severe

Endpoint

Autonomic Degeneration Index (ADI)

XII. COGNITIVE-BEHAVIORAL PANEL

Tier 10 Functional Layer

Endpoint	Normal	Mild	Moderate	Severe
MoCA	≥26	22–25	16–21	<16
MMSE	28–30	24–27	18–23	<18
Trail Making B	<75 sec	75–120	120–180	>180
CDR Global Score	0	0.5	1–2	3
NPI	Minimal	Mild	Moderate	Severe

Endpoint

Neurodegenerative Performance Score (NPS)

XIII. SCF ACUPUNCTURE RESPONSE FORECAST PANEL

Biomarker Pattern	Connectomic Fault	Acupuncture Network
pTau217 + Aβ42/40 Abnormal	Alzheimer’s-type degeneration	GV20 + GV24 + Sishencong
α-Synuclein ↑	Lewy/Parkinsonian degeneration	GB20 + GV20 + ST36
GFAP + YKL40 ↑	Neuroimmune degeneration	ST36 + LI11 + PC6
HRV ↓	Brainstem-autonomic degeneration	PC6 + HT7 + CV17
Hippocampal Atrophy	Memory network collapse	GV20 + EX-HN1 + HT7
Sleep/Glymphatic Failure	Clearance dysfunction	Anmian + HT7 + KI3
Mitochondrial Dysfunction	Bioenergetic failure	ST36 + SP6 + KI3
Limbic Dysfunction	Behavioral dysregulation	HT7 + Yintang + LV3

XIV. SCF PRECISION FORECAST MODEL

Low-Risk Progression

Criteria:

NfL <20
GFAP <250
MoCA >24
Preserved connectivity

Expected outcome:

Slow progression

Intermediate Progression

Criteria:

NfL 20–50
GFAP 250–500
Moderate hippocampal atrophy

Expected outcome:

Moderate progression

High-Risk Progression

Criteria:

NfL >50
GFAP >500
Severe connectomic fragmentation
MoCA <18

Expected outcome:

Rapid neurodegenerative decline

XV. COMPOSITE SCF NEURODEGENERATIVE ENCEPHALOPATHY SCORE (SCF-NDES)

Domain	Weight
Proteinopathy	20%
Synaptic Degeneration	15%
Neuroaxonal Injury	15%
Neuroimmune Activation	10%
Glymphatic Failure	10%
Neurovascular Dysfunction	10%
Mitochondrial Function	5%
Connectomics	10%
Autonomics	3%
Cognitive Function	2%

Interpretation

Score	Classification
<20	Stable
20–40	Mild Neurodegenerative Connectomic Dysfunction
40–60	Moderate Degeneration
60–80	Severe Neurodegenerative Encephalopathy
>80	End-Stage Connectomic Failure

XVI. PRIMARY FDA-ALIGNED CLINICAL ENDPOINTS

Diagnostic-Support Endpoints

Plasma pTau217
Aβ42/40 Ratio
MRI volumetrics
Neuropsychological testing
EEG

Predictive Endpoints

NfL
GFAP
Hippocampal atrophy rate
rs-fMRI connectivity
HRV

Therapeutic Response Endpoints

Slowed NfL rise
Stabilized GFAP
Improved cognitive scores
Improved HRV
Stabilized Connectomic Degeneration Index

NEXT PANEL IN SEQUENCE

SCF-ECCA-PRION-BIO-0010

Prion Encephalopathy Biomarker Panel

(Rapid Neurodegenerative Connectomic Collapse Validation System)

MASTER REGISTRY INDEX

SCF-ECCA-NDEG-BIO-0009 — Neurodegenerative Encephalopathy Biomarker Panel
SCF-ECCA-NDEG-ACU-0009 — Neurodegenerative Encephalopathy Acupoint Neuro-Circuit Mapping Atlas
SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
SCF-BIOMARKER-ENDPOINTS-0001 — SCF Biomarker Endpoint Validation Framework
SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema
SCF-CONNECTOMIC-DEGENERATION-0001 — Progressive Neurodegenerative Reconstruction Framework