Dynamin protein in stroke and vascular dementia.
Damage to sub-cortical white matter is a key substrate of vascular dementia (VaD) leading to deficits in executive function and cognitive processing speed. Dynamin1 is a 100 kDa protein, accounting for 0.4% of the total brain protein, and has a central role in many intracellular processes such as synaptic vesicle trafficking and recycling. In this study, we examined the status of Dynamin1 in the white matter from frontal cortex area. In order to measure the levels of Dynamin1, we isolated cortical white matter from a total of 34 post-mortem brains derived from controls (N=11), mixed Alzheimer's disease (AD) and VaD (N=8), VaD (N=7), and stroke no dementia (SND, N=8) subjects. A commercial ELISA kit was then used to determine the level of Dynamin1. In comparison to controls, Dynamin1 was elevated in patients SND (+400%) and reduced in patients with mixed VaD (-50%). Furthermore, levels of Dynamin1 were significantly associated with preserved cognition as indicated by the MMSE and CAMCOG and upregulation of vesicular glutamate transporter 1. This work indicates that Dynamin1 is associated with both preserved cognition and regenerative responses in older people with cerebrovascular disease and may represent a novel treatment target.
King's College London, Wolfson Centre for Age Related Diseases, London, UK.
Ezra
E
Mulugeta
King's College London, Wolfson Centre for Age Related Diseases, London, UK. Electronic address: julie.vallortigara@kcl.ac.uk.
Julie
J
Vallortigara
King's College London, Wolfson Centre for Age Related Diseases, London, UK.
Paul T
PT
Francis
King's College London, MRC Centre for Neurodegeneration Research, London, UK.
Abdul
A
Hye
Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK.
Rajesh N
RN
Kalaria
Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK.
Elaine K
EK
Perry
King's College London, MRC Centre for Neurodegeneration Research, London, UK.
Simon
S
Lovestone
King's College London, Wolfson Centre for Age Related Diseases, London, UK.
Clive G
CG
Ballard
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000523:psychology; D016022:Case-Control Studies; D003071:Cognition; D015140:Dementia, Vascular / Q000378:metabolism* / Q000523:psychology; D034284:Dynamin I / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008297:Male; D020521:Stroke / Q000378:metabolism* / Q000523:psychology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D050598:Vesicular Glutamate Transport Protein 1; D034284:Dynamin I
Alzheimer's disease; Frontal cortex; Stroke; Vascular dementia; White matter