Alzheimer’s disease processes start decades before it is clinically detectable

Alzheimer’s disease processes start many years before it is detected — if we were able to detect these changes early on we may increase the effectiveness of new treatments. But, we must first have validated biomarkers that are specific and sensitive enough before we can use them as surrogate markers in clinical trials or as diagnostic markers in the clinic.

Bateman et al. 2012, compared a range of markers between mutation carriers and non-carriers as a function of parental age at onset to evaluate the cascade of events that lead to dementia. This was the first international cohort of families with autosomal dominant Alzhimer’s disease.

Participants at risk for carrying a mutation for autosomal dominant Alzheimer’s disease (n=128) were assessed for clinical (Clinical Dementia Scale [CDR]), cognitive (neurophychological tests [e.g., MMSE]), imaging (volumetric MRI, FDG-PET, PIB-PET), and biochemical (e.g., CSF Ab1-42, total tau, phosphorylated tau) assessments.

In summary, significant differences in the assessments were found between carriers and non-carriers at the following years before onset:

  • Years before onset; carriers vs. non-carriers:
    •  25 years; a decrease in Ab42 concnetration in CSF
    • 15 years; an increase in deposition by PIB-PET
    • 10 years; cerebral hypometabolism
    • 5 years; cognitive impairment

These findings help to establish the time and order of changes that take place before the development of dementia, and suggest that diagnosis is made late in the course of autosomal dominant Alzheimer’s disease.

Authors note that the cross-sectional design does not represent individual longitudinal changes, and, furthermore, autosomal dominant Alzheimer’s disease represents only 1% of the Alzheimer’s disease population.

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