Encephalopathy Connectomic Collapse Atlas (ECCA-PRION) | Prion Encephalopathy Biomarker Panel

SCF-ECCA-PRION-BIO-0010

Prion Encephalopathy Biomarker Panel

Rapid Neurodegenerative Connectomic Collapse Validation System

FDA-Aligned Endpoint Framework for Precision Acupuncture Planning

Encephalopathy Connectomic Collapse Atlas (ECCA-PRION)

I. PURPOSE

The SCF Prion Encephalopathy Biomarker Panel is designed to:

Establish prion encephalopathy diagnostic support
Quantify ultra-rapid connectomic collapse
Differentiate prion disease from other dementias
Measure neurodegenerative acceleration
Predict neurologic decline and survival
Stratify supportive neuromodulation planning
Support FDA-aligned translational endpoint development
Forecast terminal network failure trajectories

II. ETIOPATHOGENIC CORE

Prion encephalopathies are characterized by:

Misfolded prion protein propagation
Self-amplifying protein templating
Synaptic destruction
Massive neuronal loss
Astrocytic activation
Spongiform degeneration
Rapid connectomic disintegration
Brainstem-autonomic failure
Global cortical collapse

Major Disease Classes

Prion Syndrome	Dominant Form
Sporadic CJD	PrPSc
Familial CJD	PRNP mutation
Variant CJD	BSE-associated
Gerstmann–Sträussler–Scheinker	PRNP mutation
Fatal Familial Insomnia	Thalamic prionopathy
Kuru-like syndromes	Historical transmissible forms

III. PRION PROPAGATION PANEL

Tier 1 Primary Disease Driver Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
RT-QuIC Prion Seeding Activity	RT-QuIC	Negative	Positive	High	Very High
PrPSc Burden	RT-QuIC/Research	Negative	Low	Moderate	High
PRNP Mutation Status	Genotyping	Negative	Variant	Pathogenic	High-risk genotype
CSF Prion Amplification Index	RT-QuIC	Negative	Positive	High	Very High

Endpoint

Prion Propagation Index (PPI)

IV. RAPID NEURODEGENERATION PANEL

Tier 2 Accelerated Neuronal Loss Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Total Tau	Simoa	<2 pg/mL	Elevated	High	Extremely High
NfL	Simoa	<10 pg/mL	20–50	50–100	>100
NSE	CLIA	<12 ng/mL	12–25	25–50	>50
UCH-L1	ELISA	<100 pg/mL	Elevated	High	Very High
Neurogranin	ELISA	Normal	Elevated	High	Very High

Endpoint

Rapid Neurodegeneration Index (RNI)

V. GLIAL ACTIVATION PANEL

Tier 3 Astrocytic Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
GFAP	Simoa	<120 pg/mL	250–500	500–1000	>1000
YKL-40	ELISA	<60 ng/mL	100–150	150–250	>250
sTREM2	ELISA	Normal	Elevated	High	Very High
MCP-1	Multiplex	Normal	Elevated	High	Very High

Endpoint

Prion Neuroglial Collapse Score (PNCS)

VI. SPONGIFORM DEGENERATION PANEL

Tier 4 Structural Destruction Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
MRI Cortical Ribboning	DWI MRI	None	Focal	Multifocal	Diffuse
Basal Ganglia Hyperintensity	MRI	None	Mild	Moderate	Severe
Thalamic Pulvinar Sign	MRI	Absent	Present	Strong	Extensive
Cortical Atrophy Rate	MRI Volumetrics	Normal	Mild	Moderate	Severe

Endpoint

Spongiform Degeneration Index (SDI)

VII. CONNECTOMIC COLLAPSE PANEL

Tier 5 Network Failure Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
EEG Periodic Sharp Wave Complexes	EEG	Absent	Rare	Frequent	Continuous
EEG Connectivity	qEEG	Normal	↓10%	↓25%	↓50%
rs-fMRI Connectivity	MRI	Normal	↓25%	↓50%	↓75%
DTI Fractional Anisotropy	MRI-DTI	Normal	↓10%	↓20%	↓40%

Endpoint

Prion Connectomic Collapse Index (PCCI)

VIII. MITOCHONDRIAL FAILURE PANEL

Tier 6 Bioenergetic Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Lactate/Pyruvate Ratio	LC-MS/MS	<20	20–30	30–40	>40
ATP Production	Seahorse	Normal	↓25%	↓50%	↓75%
CoQ10	LC-MS/MS	Normal	Mild Deficit	Moderate	Severe
cf-mtDNA	qPCR	Low	Elevated	High	Very High

Endpoint

Prion Bioenergetic Failure Index (PBFI)

IX. AUTONOMIC FAILURE PANEL

Tier 7 Brainstem-Thalamic Layer

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

Endpoint

Prion Autonomic Failure Index (PAFI)

X. COGNITIVE-NEUROPSYCHIATRIC PANEL

Tier 8 Functional Collapse Layer

Endpoint	Normal	Mild	Moderate	Severe
MoCA	≥26	22–25	16–21	<16
MMSE	28–30	24–27	18–23	<18
CDR	0	0.5	1–2	3
Myoclonus Burden	None	Mild	Moderate	Severe
Akinetic-Rigid Severity	None	Mild	Moderate	Severe

Endpoint

Prion Functional Collapse Score (PFCS)

XI. SURVIVAL FORECAST PANEL

Tier 9 Prognostic Layer

Biomarker	Low Risk	Intermediate Risk	High Risk
RT-QuIC	Weak Positive	Positive	Strong Positive
Tau	Elevated	High	Extremely High
NfL	<50	50–100	>100
EEG PSWC	Absent	Intermittent	Continuous
MRI Ribboning	Focal	Multifocal	Diffuse

Endpoint

Prion Survival Forecast Index (PSFI)

XII. SCF ACUPUNCTURE RESPONSE FORECAST PANEL

Biomarker Pattern	Connectomic Fault	Acupuncture Network
Tau + NfL ↑	Rapid neuronal collapse	GV20 + GV24 + Sishencong
GFAP + YKL-40 ↑	Astroglial activation	ST36 + LI11
HRV ↓	Brainstem-autonomic failure	PC6 + HT7 + CV17
Sleep architecture loss	Thalamic dysfunction	HT7 + KI3 + Anmian
EEG network collapse	Global connectomic failure	GV20 + EX-HN1
Limbic dysregulation	Behavioral dysfunction	HT7 + Yintang + LV3

Clinical Note: No evidence currently supports acupuncture as disease-modifying therapy for prion diseases. Any neuromodulation application would be supportive/palliative only.

XIII. SCF PRECISION FORECAST MODEL

Low-Risk Progression

Criteria:

Weak RT-QuIC positivity
NfL <50
Preserved EEG connectivity

Expected Outcome:

Slower progression phenotype

Intermediate Progression

Criteria:

Moderate RT-QuIC activity
NfL 50–100
Multifocal MRI abnormalities

Expected Outcome:

Progressive neurologic deterioration

High-Risk Progression

Criteria:

Strong RT-QuIC activity
NfL >100
Diffuse cortical ribboning
Continuous PSWC pattern

Expected Outcome:

Rapid terminal connectomic failure

XIV. COMPOSITE SCF PRION ENCEPHALOPATHY SCORE (SCF-PES)

Domain	Weight
Prion Propagation	25%
Rapid Neurodegeneration	20%
Glial Activation	10%
Spongiform Degeneration	15%
Connectomics	15%
Mitochondrial Function	5%
Autonomics	5%
Functional Status	5%

Interpretation

Score	Classification
<20	Early Disease
20–40	Mild Connectomic Failure
40–60	Moderate Progressive Collapse
60–80	Severe Prion Encephalopathy
>80	Terminal Connectomic Failure

XV. PRIMARY FDA-ALIGNED CLINICAL ENDPOINTS

Diagnostic-Support Endpoints

CSF RT-QuIC
Brain MRI (DWI/FLAIR)
EEG
Neurologic examination
PRNP genotyping (when indicated)

Predictive Endpoints

NfL
Total Tau
MRI ribboning burden
EEG PSWC burden
HRV

Therapeutic Response Endpoints

At present there are no established disease-modifying therapeutic response biomarkers for prion disease. Supportive monitoring endpoints include:

Functional decline rate
Autonomic stability
Cognitive trajectory
Care-dependency progression

NEXT PANEL IN SEQUENCE

SCF-ECCA-TOX-BIO-0011

Toxic Encephalopathy Biomarker Panel (Advanced Precision Edition)

(Toxicometabolic Connectomic Collapse Validation System)

MASTER REGISTRY INDEX

SCF-ECCA-PRION-BIO-0010 — Prion Encephalopathy Biomarker Panel
SCF-ECCA-PRION-ACU-0010 — Prion 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-PRION-CONNECTOMIC-COLLAPSE-0001 — Rapid Neurodegenerative Connectomic Collapse Framework