AB42 is a variety of amyloid protein fragment that is more likely to aggregate into small clusters and eventually into the plaques that are considered a hallmark of the Alzheimer brain.

Some researchers believe that flaws in processes governing production, accumulation, or disposal of amyloid protein in the brain are the primary cause of Alzheimer's. AB42 is a particularly "sticky" variety of amyloid protein fragment that is more likely to aggregate into small clusters and eventually into the plaques that are considered one hallmark of the Alzheimer brain.

Anne M. Fagan, PhD, of the Washington University School of Medicine, St. Louis, MO, and colleagues previously demonstrated in a small group (n=24) that a low level of AB42 in cerebrospinal fluid (CSF) is an effective marker for determining the presence of amyloid in the brain as assessed by PET scans using a marker called Pittsburgh Compound B (PIB).

In a new study presented at ICAD 2008, Fagan reported on a much larger cohort (n=132; age 45-88 years, mean 65.7). This group included individuals who were non-demented plus those with very mild or mild dementia. Consistent with the prior study, the researchers observed a striking inverse relation between presence of amyloid in the brain and levels of AB42 in CSF.

Overall, those people with high amounts of brain amyloid (as indicated by PET scan images showing positive PIB-binding) had low CSF AB42 (36/37, 97 per cent). Those with low levels of brain amyloid (negative PIB-binding) had high CSF AB42 (80/95, 84 per cent). This was true regardless of cognitive status, indicating excellent sensitivity of CSF AB42 for identifying the presence of brain amyloid, according to the researchers.

In addition, they observed that three non-demented, low CSF AB42, PIB-positive study participants have subsequently received an Alzheimer's diagnosis suggesting that positive PIB and low CSF AB42 may be useful as markers of "preclinical Alzheimer's" (that is, Alzheimer's prior to visible symptoms).

"We found that CSF AB42 is an excellent marker for identifying the presence of amyloid in the brain, regardless of the person's cognitive status," Fagan said. "Our analyses also suggest that a decline in CSF AB42 may effectively identify non-demented individuals who are in the preclinical stage of Alzheimer's, even before they are PIB positive."