The 'a, b, c's of pretangle tau and their relation to aging and the risk of Alzheimer's Disease

Braak has described the beginnings of Alzheimer's Disease as occurring in the locus coeruleus. Here we review these pretangle stages and relate their expression to recently described normal features of tau biology. We suggest pretangle tau depends on characteristics of locus coeruleus operation that promote tau condensates. We examine the timeline of pretangle and tangle appearance in locus coeruleus. We find catastrophic loss of locus coeruleus neurons is a late event. The strong relationship between locus coeruleus neuron number and human cognition underscores the utility of a focus on locus coeruleus. Promoting locus coeruleus health will benefit normal aging as well as aid in the prevention of dementia. Two animal models offering experimental approaches to understanding the functional change initiated by pretangles in locus coeruleus neurons are discussed.

Automated summary

Braak describes the onset of Alzheimer's Disease in the locus coeruleus, focusing on the pretangle stages and their connection to tau biology. Pretangle tau in locus coeruleus is believed to be influenced by the operational characteristics of the area. Understanding the timeline of pretangle and tangle formation in locus coeruleus is important for preventing cognitive decline and dementia. Promoting the health of locus coeruleus neurons can have positive effects on normal aging and cognitive function.