Study Looks at Cerebrospinal Fluid's Accuracy in Predicting Alzheimer's Disease

Researchers from the University of Gothenburg in Sweden determined β-amyloid 42 (Aβ42) cerebrospinal fluid (CSF) levels can act as predictor for Alzheimer’s disease (AD).

Previous research has speculated about apolipoprotein E (APOE) ε4 allele’s role in determining if CSF biomarkers affect AD development. Specifically, scientists have looked at its implications on Aβ42 levels, and if the alleles’ relationship to these CSF biomarkers is dependent on cortical Aβ activity.

Their study published in JAMA Psychiatry analyzed 3 groups of patients:

● Cohort A: 1,345 individuals aged 23 to 99 years with baseline CSF samples. Of the 1,345 participants, 309 had AD, 287 had prodromal AD, 399 with stable mild cognitive impairment (MCI), 99 with a dementia other than AD, and 251 controls

● Cohort B: 105 individuals, aged 20-34 years without dementia and available CSF readings

● Cohort C: 118 patients aged 60-80 years exhibiting mild cognitive symptoms who underwent flutemetamol F18 ([18F] flumetamol) positron emission tomography amyloid imaging and a CSF tap

The investigators found that CSF levels of Aβ42 were lower in APOE ε4 carriers than in non-carriers, and also noted Aβ42 levels were different among AD patients compared to controls and MCI subjects. Furthermore, the gene was found not to determine Aβ42 levels in younger individuals.

“We clearly verified that APOE ε4 genotype is associated with lower CSF levels of Aβ42 but not T-tau and P-tau in a gene dose — dependent manner, which is in agreement with earlier studies,” penned the writers. “However, all 3 biomarkers showed significant differences between AD patients and controls and between MCI-AD and stable MCI patients irrespective of APOE genotype.”

Based on their discovery that CSF levels of Aβ42 and APOE ε4 acted as independent predictors of AD, the investigators determined the “clinical cutoff” for Aβ42 levels should be same regardless of APOE carrier-status.