New indications for the earliest brain changes in Alzheimer's disease

Betty Tijms and colleagues published in Annals of Neurology this month that normal amyloid marks in cerebrospinal fluid (CSF) do not exclude incident Alzheimer’s disease (AD).

Decreased levels of amyloid β 1-42 in cerebrospinal fluid (CSF) are a robust marker for Alzheimer’s disease (AD) and indicate the presence of amyloid plaques in the brain. Still, 15-30% of people who have mild cognitive impairment and normal amyloid develop an AD type of dementia. We analysed normal amyloid β 1-42 levels in non-demented memory clinic patients and observed that a range of normal values exist that is associated with an up to 21 fold increased risk show cognitive decline over time. 

These results indicate that in non-demented people normal amyloid β 1-42 values should be taken into account when studying the earliest changes in the brain that are relevant for AD.  


FIGURE: Survival curves for the time to clinical progression in nondemented subjects. pMCI = subjects with mild cognitive impairment who showed clinical progression; pSCD = subjects with subjective cognitive decline who showed clinical progression. Separate lines indicate progression according to quintiles of cerebrospinal fluid amyloid β 1-42 levels.