Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 145

The aggregation of misfolded proteins is a characteristic feature of neurodegenerative disorders (e.g. AD, PD, frontotemporal dementias, Lewy body dementia, amyotrophic lateral sclerosis) and the normal ageing process.¹⁹ Various clinicopathological studies have shown that altered proteins like hyperphosphorylated‐tau, amyloid‐β, α‐synuclein, and TDP‐43 can also be found in the brain of cognitively normal and relatively healthy older individuals.^19–21 Interestingly, these protein alterations are rarely isolated and can result in a wide array (i.e. more than 230) of combined or mixed neuropathologies in subjects presenting or not presenting the phenotypic manifestations of underlying neurodegenerative processes.²² These observations highlight an important question: Would elderly individuals with AD‐related/PD‐related pathologies ever have developed dementia/PD later in their lives? Alternatively, might these individuals have lived well beyond a normal lifespan without neurologic symptoms because of, not despite, AD/PD pathology?¹⁹ In other words, could we consider protein accumulation not pathogenic per se, but rather a compensatory or even protective mechanism for the brain? The answer to this question will allow the development of targeted therapeutic strategies to slow or even stop neurodegenerative processes.