Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about ALZHEIMER'S DISEASE: 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.
Alzheimer's disease (AD) is the leading cause of dementia worldwide, characterized by progressive cognitive decline, memory impairment, and personality changes. The amyloid cascade hypothesis posits that accumulation of amyloid-beta peptides triggers tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and neuronal death. Recent approvals of anti-amyloid antibodies (lecanemab, donanemab) mark a new era in AD treatment.
| Gene Symbol | ALZHEIMER'S DISEASE |
| Lipid raft disruption | Alterations in membrane sphingolipid composition affect amyloid precursor protein (APP) processing and amyloid-beta production |
| Neuroinflammation | Ceramide activates pro-inflammatory pathways in microglia and astrocytes |
| Autophagy dysregulation | Sphingolipid accumulation impairs autophagosome-lysosome fusion-lysosome-pathway) |
| Synaptic dysfunction | Ganglioside alterations disrupt synaptic vesicle trafficking and receptor signaling |
| Focus | Ganglioside-based neuroprotection therapies |
| Lead Candidate | Trappsol (cyclodextrin) — Phase 3 in Niemann-Pick Type C, being explored in Alzheimer's disease |
| Indication | Alzheimer's disease (preclinical) |
| Pipeline | Trappsol administered intravenously, with clinical trials in Alzheimer's disease expected to initiate in 2025-2026 |
| Notable | Focuses on the balance between pro-apoptotic long-chain ceramides (C16-C24) and neuroprotection very-long-chain ceramides (C26+) |
| Mechanism | Develops small molecules targeting ceramide synthases (CerS) and sphingosine kinases (SK1/SK2). Key targets include: |
| Stage | Lead optimization |
| Scientific Foundation | Founded by researchers from the Van Andel Institute with deep expertise in sphingolipid biochemistry and neurodegenerative disease |
| Associated Diseases | ALS, AMYLOID PLAQUES, AMYOTROPHIC LATERAL SCLEROSIS, ATHEROSCLEROSIS, AUTISM, Aging |
| Known Drugs/Compounds | LECANEMAB, RESVERATROL, CURCUMIN, RAPAMYCIN, MEMANTINE, QUERCETIN |
| Interactions | P62, SYNAPTIC PRUNING, FERROPTOSIS, NEURODEGENERATIVE DISORDERS, SQSTM1, AUTOPHAGY |
| KG Connections | 7323 knowledge graph edges |
| Databases | GeneCardsUniProtNCBI GeneHPASTRING |
Knowledge base pages for this entity
graph TD
subgraph Pathology["Pathology"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"associated with"| Alzheimer["Alzheimer"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"associated with"| Neurodegeneration["Neurodegeneration"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"contributes to"| Als_3["Als"]
AMYLOID_BETA["AMYLOID-BETA"] -->|"associated with"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
TAU["TAU"] -->|"associated with"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
MITOPHAGY["MITOPHAGY"] -->|"associated with"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
NEURODEGENERATION["NEURODEGENERATION"] -->|"associated with"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
end
subgraph Signaling["Signaling"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"regulates"| Als["Als"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"regulates"| Alzheimer_1["Alzheimer"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"activates"| Neurodegeneration_2["Neurodegeneration"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"regulates"| Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"activates"| Autophagy["Autophagy"]
ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"activates"| Apoptosis["Apoptosis"]
NEURODEGENERATION_5["NEURODEGENERATION"] -->|"activates"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
end
subgraph Interactions["Interactions"]
MITOPHAGY_4["MITOPHAGY"] -->|"protects against"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
end
style ALZHEIMER_S_DISEASE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
style Alzheimer fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Neurodegeneration fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Alzheimer_1 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Neurodegeneration_2 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als_3 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Amyotrophic_Lateral_Sclerosis fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Autophagy fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Apoptosis fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style AMYLOID_BETA fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style TAU fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style MITOPHAGY fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style MITOPHAGY_4 fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style NEURODEGENERATION fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style NEURODEGENERATION_5 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0| Target | Relation | Type | Str |
|---|---|---|---|
| Alzheimer | associated_with | disease | 1.00 |
| Als | regulates | disease | 1.00 |
| Neurodegeneration | associated_with | disease | 1.00 |
| Alzheimer | regulates | disease | 1.00 |
| Neurodegeneration | activates | disease | 1.00 |
| Als | contributes_to | disease | 1.00 |
| Amyotrophic Lateral Sclerosis | regulates | disease | 1.00 |
| Autophagy | activates | pathway | 1.00 |
| Apoptosis | activates | pathway | 1.00 |
| Als | inhibits | disease | 1.00 |
| AKT | activates | gene | 1.00 |
| NEUROINFLAMMATION | therapeutic_target | gene | 1.00 |
| Dementia | contributes_to | disease | 1.00 |
| Inflammation | therapeutic_target | disease | 1.00 |
| Alzheimer | therapeutic_target | disease | 1.00 |
| Als | activates | disease | 1.00 |
| Neuroinflammation | therapeutic_target | disease | 1.00 |
| Mitophagy | activates | pathway | 1.00 |
| Mtor | activates | pathway | 1.00 |
| Aging | associated_with | disease | 1.00 |
| Tauopathy | activates | disease | 1.00 |
| Aging | therapeutic_target | disease | 1.00 |
| Als | therapeutic_target | disease | 1.00 |
| Autophagy | therapeutic_target | pathway | 1.00 |
| Mtor | therapeutic_target | pathway | 1.00 |
| TAU | activates | gene | 1.00 |
| Oxidative Stress | activates | pathway | 1.00 |
| MITOCHONDRIAL DYSFUNCTION | associated_with | gene | 1.00 |
| Diabetes | associated_with | disease | 1.00 |
| Cancer | therapeutic_target | disease | 1.00 |
| Diabetes | therapeutic_target | disease | 1.00 |
| Oxidative Stress | therapeutic_target | pathway | 1.00 |
| Dementia | activates | disease | 1.00 |
| TAU | associated_with | gene | 1.00 |
| Dementia | associated_with | disease | 1.00 |
| Als | expressed_in | disease | 1.00 |
| Alzheimer | interacts_with | disease | 1.00 |
| Alzheimer | activates | disease | 1.00 |
| Aging | activates | disease | 1.00 |
| Cancer | associated_with | disease | 1.00 |
| BRAIN INJURY | associated_with | gene | 1.00 |
| AKT | therapeutic_target | gene | 1.00 |
| Neurodegeneration | therapeutic_target | disease | 1.00 |
| Apoptosis | therapeutic_target | pathway | 1.00 |
| Alzheimer | inhibits | disease | 1.00 |
| TAU | regulates | gene | 1.00 |
| AUTOPHAGY | associated_with | gene | 1.00 |
| OXIDATIVE STRESS | associated_with | gene | 1.00 |
| Autophagy | associated_with | pathway | 1.00 |
| Oxidative Stress | associated_with | pathway | 1.00 |
| Source | Relation | Type | Str |
|---|---|---|---|
| AMYLOID-BETA | associated_with | gene | 1.00 |
| TAU | associated_with | gene | 1.00 |
| NEURODEGENERATION | associated_with | gene | 1.00 |
| NEURODEGENERATION | activates | gene | 1.00 |
| MITOPHAGY | activates | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | associated_with | gene | 1.00 |
| NEURODEGENERATION | therapeutic_target | gene | 1.00 |
| PARKINSON'S DISEASE | associated_with | gene | 1.00 |
| PARKINSON'S DISEASE | activates | gene | 1.00 |
| MITOPHAGY | therapeutic_target | gene | 1.00 |
| NEURODEGENERATION | inhibits | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | regulates | gene | 1.00 |
| NEURODEGENERATION | regulates | gene | 1.00 |
| NEURODEGENERATION | protects_against | gene | 1.00 |
| NEURODEGENERATION | expressed_in | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | therapeutic_target | gene | 1.00 |
| NEURODEGENERATION | contributes_to | gene | 1.00 |
| PARKINSON'S DISEASE | therapeutic_target | gene | 1.00 |
| TREM2 | associated_with | gene | 1.00 |
| TAU | therapeutic_target | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | activates | gene | 1.00 |
| TREM2 | activates | gene | 1.00 |
| TAU | activates | gene | 1.00 |
| TREM2 | therapeutic_target | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | expressed_in | gene | 1.00 |
| ROS | activates | gene | 1.00 |
| AMYLOID | inhibits | gene | 1.00 |
| AMYLOID | interacts_with | gene | 1.00 |
| ALZHEIMER | interacts_with | gene | 1.00 |
| AMYLOID | activates | gene | 1.00 |
| AMYLOID | biomarker_for | gene | 1.00 |
| AMYLOID | associated_with | gene | 1.00 |
| AMYLOID | causes | gene | 1.00 |
| ALZHEIMER | associated_with | gene | 1.00 |
| ASTROCYTES | activates | gene | 1.00 |
| AMYLOID | regulates | gene | 1.00 |
| AMYLOID | contributes_to | gene | 1.00 |
| APOPTOSIS | activates | gene | 1.00 |
| OXIDATIVE STRESS | activates | gene | 1.00 |
| ASTROCYTES | inhibits | gene | 1.00 |
| ALZHEIMER | biomarker_for | gene | 1.00 |
| NEURODEGENERATION | biomarker_for | gene | 1.00 |
| TAU | biomarker_for | gene | 1.00 |
| ALZHEIMER | activates | gene | 1.00 |
| ALZHEIMER | contributes_to | gene | 1.00 |
| LC3 | activates | gene | 1.00 |
| AMYLOID | expressed_in | gene | 1.00 |
| DEMENTIA | associated_with | gene | 1.00 |
| GENES | associated_with | gene | 1.00 |
| HUNTINGTON | associated_with | gene | 1.00 |
Hypotheses where this entity is a therapeutic target
Scientific analyses that reference this entity
neuroinflammation | 2026-04-15 | 1 hypotheses Top: 0.650
neurodegeneration | 2026-04-15 | 1 hypotheses Top: 0.527
neurodegeneration | 2026-04-15 | 1 hypotheses Top: 0.578
neurodegeneration | 2026-04-14 | 0 hypotheses
neuroinflammation | 2026-04-14 | 0 hypotheses
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| External fixation versus reverse shoulder arthroplasty for proximal humerus frac [PMID:41940987] | Vadalà A, Benelli C, Suraci F, Carta B, | Arch Orthop Trauma Surg | 2026 | 0 |
| Gray matter structural and molecular signatures in Alzheimer's disease and late- [PMID:41419068] | Yang S, Wang X, Yan Y, Zhang J, Wei Y et | J Affect Disord | 2026 | 0 |
| Cytomegalic parvalbumin neurons in fetal cases of hemimegalencephaly. [PMID:39973610] | Gelot AB, Draia-Nicolau TO, Mathieu R, S | Epilepsia | 2025 | 0 |
| Brain connectivity and transcriptional changes induced by rTMS in first-episode [PMID:40274783] | Guan M, Xie Y, Wang Z, Miao Y, Li X et a | Transl Psychiatry | 2025 | 0 |
| Single-cell RNA sequencing of adult primate neocortex reveals the regulatory dyn [PMID:40385068] | Zhang C, Xie Z, Wang N | Am J Transl Res | 2025 | 0 |
| Human stem cell-derived GABAergic interneuron development reveals early emergenc [PMID:40651475] | Bershteyn M, Zhou H, Fuentealba L, Chen | Neuron | 2025 | 0 |
| Enhancer AAV toolbox for accessing and perturbing striatal cell types and circui [PMID:40403704] | Hunker AC, Wirthlin ME, Gill G, Johansen | Neuron | 2025 | 0 |
| Forebrain assembloids support the development of fast-spiking human PVALB+ corti [PMID:40695284] | Walsh RM, Crabtree GW, Kalpana K, Jubier | Neuron | 2025 | 0 |
| Anterior cingulate cortex parvalbumin and somatostatin interneurons shape social [PMID:40320404] | Qi C, Sima W, Mao H, Hu E, Ge J et al. | Nat Commun | 2025 | 0 |
| Distinct dendritic integration strategies control dynamics of inhibition in the [PMID:40592329] | Morabito A, Zerlaut Y, Dhanasobhon D, Be | Neuron | 2025 | 0 |
| Targeting SARM1 improves autophagic stress-induced axonal neuropathy. [PMID:37561040] | Kim HR, Lee HJ, Jeon Y, Jang SY, Shin YK | Autophagy | 2024 | 0 |
| Integrated multimodal cell atlas of Alzheimer's disease. [PMID:39402379] | Gabitto MI, Travaglini KJ, Rachleff VM, | Nat Neurosci | 2024 | 0 |
| Identification of early Alzheimer's disease subclass and signature genes based o [PMID:39650656] | Wang W, Lu J, Pan N, Zhang H, Dai J et a | Front Immunol | 2024 | 0 |
| Cortical somatostatin long-range projection neurons and interneurons exhibit div [PMID:38086373] | Fisher J, Verhagen M, Long Z, Moissidis | Neuron | 2024 | 0 |
| Locus Coeruleus-Dorsolateral Septum Projections Modulate Depression-Like Behavio [PMID:38155473] | Zhang Q, Xue Y, Wei K, Wang H, Ma Y et a | Adv Sci (Weinh) | 2024 | 0 |
| Somatostatin and the pathophysiology of Alzheimer's disease. [PMID:38484981] | Almeida VN | Ageing Res Rev | 2024 | 0 |
| Somatostatin interneurons control the timing of developmental desynchronization [PMID:38599213] | Mòdol L, Moissidis M, Selten M, Oozeer F | Neuron | 2024 | 0 |
| De novo gene synthesis by an antiviral reverse transcriptase. [PMID:39116258] | Tang S, Conte V, Zhang DJ, Žedaveinytė R | Science | 2024 | 0 |
| Signature morphoelectric properties of diverse GABAergic interneurons in the hum [PMID:37824669] | Lee BR, Dalley R, Miller JA, Chartrand T | Science | 2023 | 0 |
| Novel App knock-in mouse model shows key features of amyloid pathology and revea [PMID:35690868] | Xia D, Lianoglou S, Sandmann T, Calvert | Mol Neurodegener | 2022 | 0 |