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.

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.

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.

Unlike sedatives, DORA-class sleep aids (Dual Orexin Receptor Antagonists) work by inhibiting wakefulness, creating more natural sleep architecture. Research suggests this may improve the brain's ability to clear beta-amyloid and tau proteins linked to Alzheimer's disease, offering a potential preventative strategy.

Auguste Deter, the first patient described with Alzheimer's, lacked the genetic risk factors for the disease. Retrospective analysis suggests her presenile dementia, which featured amyloid plaques similar to Alzheimer's, may have been caused by neurosyphilis or other factors, challenging the historical foundation of the disease's definition.

It's possible to have a brain full of amyloid plaques (a hallmark of Alzheimer's) yet show no cognitive decline. This is due to 'cognitive reserve,' the brain's ability to withstand damage. Building this reserve through activities like reading, writing, and exercise is a key defense.

Unlike sedatives like Ambien, a new class of medication (DORAs) works by dialing down the brain's wakefulness chemical (orexin). This allows for naturalistic sleep that is functionally beneficial, proven to increase the brain's cleansing of beta amyloid and tau protein, which are linked to Alzheimer's disease.

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".

Senescent cells are not inactive; they are metabolically active and secrete inflammatory molecules known as SASP (Senescence-Associated Secretory Phenotype). This initially helps clear damage, but as these cells accumulate with age, the chronic inflammation they cause can worsen diseases like Alzheimer's, heart disease, and liver fibrosis.