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Pathways common to brain development and ageing: defining strategies for preventive therapy and diagnostics

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Similarities during brain development and ageing

A European consortium is examining molecular mechanisms common during brain development and ageing to gain insight into the causes of Alzheimer's disease (AD).

Health

With an increase in the overall life expectancy, many European citizens suffer from age-related neurodegenerative conditions such as AD. Understanding the process of ageing could provide solutions for many age-related problems, including neurodegenerative disorders such as Alzheimer's. Accumulating evidence points towards shared molecular pathways between early developmental processes and ageing. Scientists of the EU-funded DEVELAGE (Pathways common to brain development and ageing: defining strategies for preventive therapy and diagnostics) project have also compared protein modification, altered cellular functions, gene expression and genetic and epigenetic alterations that take place during the development and ageing process. The DEVELAGE team compared research results with those from the brains of the non-human primate model Microcebus murinus, the grey mouse lemur, and transgenic mice. Furthermore, they examined the brain of Down's syndrome patients to discover cell alterations, dysplastic phenomena, and activation of apoptosis signalling as well as of neurodegeneration-related pathways. Affected early in AD, the researchers studied changes in the hippocampus, the seat of new memory-making. They also looked at cellular metabolite and gene transcription changes occurring before AD has fully developed. Important in any disease, epigenetic changes may play a big part in AD. Furthermore, AD does not affect all patients in the same way and the research team looked at the spectrum of effects affecting the brains of the elderly. The healthy brain, although ageing, has a protective genetic element and the scientists studied the genetic constellations associated with normal brain changes. Researchers used the grey mouse lemur as a competitive tool for research on neurodegenerative disorders. As a result, they identified a novel neurochemical signalling pathway in the central nervous system that is deregulated in several neurodegenerative diseases. All these observations support a link between developmental and degenerative pathways in neurogenesis. Collectively, the DEVELAGE project work enhanced our understanding of early pathological events in neurodegenerative disorders. Implementation of this information in the design of therapeutic interventions should help reverse neurodegenerative conditions by promoting neurogenesis.

Keywords

Brain development, ageing, molecular mechanisms, Alzheimer's disease, neurodegenerative disorders

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