Is Alzheimer's a Disorder of Ageing and Why Don't Mice get it? The Centrality of Insulin Signalling to Alzheimer's Disease Pathology

TY - CHAP

T1 - Is Alzheimer's a Disorder of Ageing and Why Don't Mice get it? The Centrality of Insulin Signalling to Alzheimer's Disease Pathology

AU - Lovestone, Simon

AU - Killick, Richard

PY - 2010

Y1 - 2010

N2 - The amyloid cascade hypothesis has had considerable importance in driving forward the molecular understanding of Alzheimer's disease (AD) pathology. One component of that cascade might be glycogen synthase kinase-3 (GSK3), a kinase that appears to be activated by A beta and in turn phosphorylates tau. GSK3 is also inhibited by insulin signalling and insulin resistance, and diabetes is a major risk factor for AD. We hypothesise, as others have done, that insulin signalling is central to the pathological process, with evidence that both genetic and environmental risk factors for AD involve the insulin pathway. We also postulate that transgenic mice provide only a partial model for AD, as insulin signalling acts as a protective factor against A beta toxicity; also, the well-established relationship between insulin signalling and longevity might explain why the single most important risk factor for AD is age.

AB - The amyloid cascade hypothesis has had considerable importance in driving forward the molecular understanding of Alzheimer's disease (AD) pathology. One component of that cascade might be glycogen synthase kinase-3 (GSK3), a kinase that appears to be activated by A beta and in turn phosphorylates tau. GSK3 is also inhibited by insulin signalling and insulin resistance, and diabetes is a major risk factor for AD. We hypothesise, as others have done, that insulin signalling is central to the pathological process, with evidence that both genetic and environmental risk factors for AD involve the insulin pathway. We also postulate that transgenic mice provide only a partial model for AD, as insulin signalling acts as a protective factor against A beta toxicity; also, the well-established relationship between insulin signalling and longevity might explain why the single most important risk factor for AD is age.

U2 - 10.1007/978-3-642-04300-0_9

DO - 10.1007/978-3-642-04300-0_9

M3 - Conference paper

SN - 978-3-642-04299-7

T3 - DIABETES, INSULIN AND ALZHEIMER'S DISEASE

SP - 129

EP - 152

BT - Unknown

PB - Springer

CY - BERLIN

T2 - 24th Symposium on Medicine and Research of Alzhemers Disease

Y2 - 6 April 2009

ER -