Diagram showing Hippocampus, an area affected by Alzheimer’s Disease (credits Appendix A)
Small and Duff’s Dual Pathway hypothesis is widely cited (e.g see here). The interested reader is referred to the paper above. However I have outlined the salient features below as I have found them
(1) The Amyloid Cascade Hypothesis does not appear to explain all cases of Alzheimer’s Disease particularly when this is late in onset.
(2) Tau gene mutations are described as leading to Frontotemporal Dementia rather than Alzheimer’s Type Dementia
(3) A dual pathway is hypothesised which describes processes upstream to the Amyloid deposition and tau phosphorylation and which influence both
(4) Small and Duff identify APOE4, GSK and the Retromer sorting pathway as three examples of upstream drivers
(5) When Amyloid deposition is absent or minimal but the other elements are present this has implications for Amyloid reducing strategies
Appendix A – Credits
Picture by FG Designs. Creative Commons License.
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