The foundational discovery of the toxic alpha-sheet structure was first identified via computer simulations because it was impossible to characterize experimentally. This computational hypothesis then required 15 years of wet lab work to validate, highlighting the power of in-silico methods to pioneer novel drug targets.

The distinction between "diseases of late life" and aging itself is artificial. Conditions like Alzheimer's or most cancers are simply aspects of aging that have been given disease-like names. This unifies them as targets for a single, comprehensive anti-aging medical intervention.

While PET scans show lower glucose uptake in Alzheimer's brains, this may not be due to insulin resistance ("type 3 diabetes"). Studies show these brains can absorb glucose normally when cognitively stimulated. This suggests the issue is a lack of demand from inactive brain regions, not a failed supply mechanism.

Frontotemporal Dementia (FTD) is tricky to diagnose because it primarily affects the frontal and temporal lobes, which control behavior and language, not memory. A person with FTD can easily pass standard cognitive tests designed for Alzheimer's, leading to dangerous misdiagnoses and delaying proper support.

A long-term study found many nuns had brains full of Alzheimer's plaques post-mortem, yet displayed no cognitive decline in life. Their constant social responsibilities and interactions acted as a continuous mental challenge, building new neural pathways that bypassed the damaged areas.

Alzheimer's can be understood as a vascular disease rooted in nitric oxide deficiency. This decline impairs blood flow, glucose uptake, and inflammation regulation in the brain. Therefore, strategies to restore nitric oxide address the physiological root causes of the disease, not just the symptoms like plaque buildup.

Voyager CEO Al Sandrock suggests the 30% average efficacy of new Alzheimer's drugs isn't uniform. Instead, some patients may see a complete halt in progression while others see no benefit. He argues the next critical step is predicting these responders, which will determine whether future therapies like anti-tau agents should be added on or used as a replacement.

After several tau-targeting antibodies failed, including J&J's pazdenimab, confidence in blocking extracellular tau is waning. The field's new hope is Biogen’s Biv80, an antisense drug that prevents tau protein production at the mRNA level, a mechanism that has shown potential to reverse pathology in early data.

Large-scale genetic studies suggest many distinct brain diseases (mania, depression, ADHD, Alzheimer's) are not separate conditions. Instead, they may be different expressions of a single, general genetic susceptibility to brain dysfunction, which researchers call "Factor P".