Selectively vulnerable neurons in Alzheimer’s disease: functional and morphological changes in healthy ageing and early Alzheimer's disease
The indcidence of Alzheimer’s disease is highly correlated with ageing, and it is known that the altered behaviour of neurons play an important role in memory loss in healthy aging. In Alzheimer’s disease severe memory deficts are caused by the dysfunction and death of a select group of neurons, yet it is not understood why these particular neurons are susceptible. Dr Woodhouse' fellowship will determine how the connections and activity of these vulnerable neurons are changed in healthy aging and early Alzheimer’s disease and aim to answer the following questions:
- Do neurons that are vulnerable in Alzheimer’s disease have a signature of changes in healthy ageing that might predispose them to be susceptible in Alzheimer’s disease?
- Do these vulnerable neurons have a distinct set of changes in their connections and activity in early Alzheimer’s disease?
- Can we identify novel targets in these vulnerable neurons for the development of new therapeutics for Alzheimer’s disease?
This fellowship will significantly advance our knowledge by producing information essential for understanding how neurons function in healthy ageing and how this is altered in the group of vulnerable neurons in Alzheimer’s disease. Understanding the mechanisms underlying the selective vulnerability of this important group of neurons in Alzheimer’s disease will potentially lead to the development of new therapeutics for Alzheimer’s disease.
Alzheimer's disease is highly correlated with ageing. Alterations in neuron function are important in age-associated cognitive decline. In Alzheimer's disease memory deficits are due to dysfunction, degeneration and death of a vulnerable subpopulation of neurons. Existing knowledge is extremely limited and does not identify why a subset of neurons are selectively vulnerable in Alzheimer's disease.
Dr Woodhouse hypothesises that vulnerable neurons in AD exhibit a distinct signature of alterations in healthy aging and early Alzheimer's disease.
A multi-dimensional approach (patch-clamp electrophysiology, morphological analysis, cognitive assessment) will be used to:
- Determine how neuronal activity, morphology and cognition are altered in neuron subpopulations in healthy ageing.
- Examine how neuronal activity and morphology are altered in vulnerable neurons in early AD.
- Identify and characterize alterations in currents underlying age- and AD-associated changes in neuronal activity.
This fellowship will significantly advance our knowledge by producing data essential for understanding how neurons function across healthy ageing and how this is altered in the subpopulation of neurons vulnerable to Alzheimer's disease, providing vital knowledge that will be valuable across key areas of neuroscience research. Understanding of the mechanisms underlying the selective vulnerability of this subset of neurons in Alzheimer's disease will inform the design of therapeutics aimed at protecting these cells.
Dr Woodhouse is based at the Wicking Dementia Research and Education Centre, University of Tasmania and will begin her two year AADRF funded fellowship in early 2015.