University College London
Determining the causes and consequences of brain amyloidosis, atrophy and cerebrovascular disease
Alzheimer's Research UK
Alzheimer's disease & other dementias
Alzheimer’s disease (AD) has a long prodromal phase when pathology accumulates before cognitive decline. Biomarkers including MRI/PET/CSF allow aspects of AD pathology to be quantified in vivo, opening a pre-symptomatic window for disease prevention strategies. It is however unknown:
(a) which factors influence beta-amyloid deposition, a critical early pathogenic step;
(b) if individuals accumulating sufficient beta-amyloid will inevitably develop AD should they live long enough and if so what influences when; and
(c) how beta-amyloid interacts with other pathologies to influence cognitive decline.
We will capitalise on the unique life-course data of the MRC 1946 birth cohort a representative,intensively studied UK cohort now in their 60s by enrolling 500 study members in a two-time-point (0,24m) study involving MRI and amyloid PET, detailed cognitive testing, wet biomarkers and genotyping.
We aim to:
(1) identify pre-symptomatic AD and associated biomarkers;
(2) investigate life-course and genetic influences on symptom onset and progression; and
(3) provide a critical evidence base for future trials.
This work will inform pre-clinical AD therapeutic study design: from inclusion criteria to outcome measures. Risk factors identified may be targets for drug development, and may already be amenable to modification.