This synthesis consolidates therapeutic targets across Alzheimer's disease (AD), Parkinson's disease (PD), ALS, and FTD to identify target families with cross-disease relevance. By grouping targets into families based on pathway membership and biological function, we can prioritize opportunities where a single therapeutic approach may benefit multiple neurodegenerative conditions.
This analysis complements our Therapeutic Approach Evidence Rankings, Investment Signal Synthesis, Cross-Disease Shared Pathways Synthesis, and Gene-Mechanism-Therapy Causal Chains by providing a target-family perspective on therapeutic development.
We define target families as groups of proteins/genes that share:
| Target | Disease | Evidence Score | Development Stage | Cross-Disease Potential |
|---|---|---|---|---|
| TFEB | AD/PD | 8.5 | Phase 1 | High — master regulator |
| GBA/GCase | PD | 9.0 | Phase 2-3 | Moderate — specific to GBA |
| LRRK2 | PD | 8.5 | Phase 2 | Low — PD-specific |
| VPS35 | AD | 7.0 | Preclinical | Moderate — retromer function |
| ATG proteins | ALS | 6.5 | Preclinical | Moderate — autophagy genes |
Cross-Disease Assessment: High consolidation opportunity — TFEB activation enhances clearance of Aβ, α-syn, and TDP-43 in preclinical models[1].
| Target | Disease | Evidence Score | Development Stage | Cross-Disease Potential |
|---|---|---|---|---|
| TREM2 | AD/FTD | 9.0 | Phase 2b | High — microglial activation |
| NLRP3 | AD/PD | 8.0 | Phase 1-2 | High — common pathway |
| cGAS-STING | AD/PD/ALS | 7.5 | Phase 1 | High — type I IFN common |
| CD33 | AD | 6.5 | Preclinical | Moderate — microglial receptor |
| TNF-alpha | PD/ALS | 6.0 | Preclinical | Moderate — inflammatory cascade |
Cross-Disease Assessment: Strong consolidation — neuroinflammation is a shared feature across all neurodegenerative diseases[2].
| Target | Disease | Evidence Score | Development Stage | Cross-Disease Potential |
|---|---|---|---|---|
| GLP-1/GIP Receptor | AD/PD | 9.5 | Phase 3 | Very High — neuroprotection |
| mTOR | AD/PD/ALS | 7.0 | Preclinical | High — protein homeostasis |
| AMPK | AD/PD | 6.5 | Preclinical | High — energy sensing |
| NAD+/SIRT1 | AD/PD | 7.0 | Phase 1-2 | High — mitochondrial function |
Cross-Disease Assessment: Very high consolidation — metabolic dysfunction is a convergent feature across neurodegenerative diseases[3].
| Target | Disease | Evidence Score | Development Stage | Cross-Disease Potential |
|---|---|---|---|---|
| Aβ | AD | 9.5 | Approved | Low — disease-specific |
| Tau | AD/PSP | 9.0 | Phase 2-3 | Moderate — 4R-tau specific |
| α-Syn | PD/DLB | 8.5 | Phase 2-3 | Low — disease-specific |
| TDP-43 | ALS/FTD | 8.0 | Preclinical | Moderate — ALS/FTD shared |
| SOD1 | ALS | 9.0 | Approved | Low — gene-specific |
Cross-Disease Assessment: Low consolidation — aggregation is disease-specific despite common proteostatic mechanisms.
| Target | Disease | Evidence Score | Development Stage | Cross-Disease Potential |
|---|---|---|---|---|
| GSK-3β | AD | 7.5 | Phase 2 | Moderate — tau phosphorylation |
| c-Abl | PD | 6.5 | Phase 2 | Low — alpha-syn phosphorylation |
| CDK5 | AD/PD | 6.0 | Preclinical | Moderate — tau/α-syn |
| DLK/MAP3K12 | ALS | 5.5 | Preclinical | Low — axon degeneration |
Cross-Disease Assessment: Moderate consolidation — multiple kinases converge on similar substrates.
| Rank | Target Family | Primary Targets | Cross-Disease Score | Recommendation |
|---|---|---|---|---|
| 1 | GLP-1/GIP Signaling | GLP-1R, GIPR | 9.5 | Fast-track — Phase 3 readouts |
| 2 | TREM2 Modulation | TREM2, ligands | 9.0 | Priority — microglial focus |
| 3 | NLRP3 Inflammasome | NLRP3, ASC, caspase-1 | 8.5 | Priority — common pathway |
| 4 | cGAS-STING Pathway | cGAS, STING, TBK1 | 8.0 | Investigate — early stage |
| 5 | TFEB Autophagy Activation | TFEB, mTORC1 | 8.0 | Investigate — master regulator |
| Rank | Target Family | Primary Targets | Cross-Disease Score | Recommendation |
|---|---|---|---|---|
| 6 | NAD+ Metabolism | SIRT1, PARP, NMNAT | 7.5 | Monitor — biomarker data |
| 7 | TDP-43 Pathology | TDP-43, FUS, hnRNPs | 7.5 | Monitor — ALS/FTD focus |
| 8 | Iron Metabolism | ferroportin, hepcidin | 6.5 | Research — emerging |
| 9 | Myelin/Axonal Integrity | MBP, PLP, neurofilament | 6.5 | Research — biomarker link |
Top Target Families:
Top Target Families:
Top Target Families:
| Target Family | Investment Level | Evidence | Priority |
|---|---|---|---|
| GLP-1/GIP | $2B+ | High | Immediate |
| TREM2 | $1B+ | High | Near-term |
| α-Syn immunotherapy | $700M+ | Moderate | Near-term |
| NLRP3 | $220M+ | Moderate | Medium-term |
| Target Family | Investment Gap | Opportunity |
|---|---|---|
| TFEB activation | $50M | High potential — master regulator |
| cGAS-STING | $80M | Novel mechanism — common pathway |
| NAD+ boosters | $60M | Biomarker data emerging |
| TDP-43 modulators | $40M | ALS/FTD consolidation |