Cerebrospinal Fluid Aβ43 Is Reduced in Early-Onset Compared to Late-Onset Alzheimer's Disease, But Has Similar Diagnostic Accuracy to Aβ42

Background: Amyloid beta 1-43 (A beta 43) may be a useful additional biomarker for diagnosing Alzheimer's disease (AD). We have investigated cerebrospinal fluid (CSF) levels of A beta 43 in patients with early-onset AD in contrast to levels in late-onset AD. For comparison, in addition to the 'core' biomarkers, several other analytes were also determined [YKL-40, neurofilament light (NF-L), glial fibrillary acidic protein (GFAP), and progranulin]. Material and Methods: Cerebrospinal fluid samples were obtained from patients with early-onset AD (age <= 62, n = 66), late-onset AD (age >= 68, n = 25), and groups of cognitively intact individuals (age <= 62, n = 41, age >= 68, n = 39). Core CSF AD biomarkers [amyloid beta 1-42 (A beta 42), total tau, phosphorylated tau] were analyzed, as well as levels of A beta 43 and other analytes, using commercially available enzyme-linked immunosorbent assays. Results: Cerebrospinal fluid Ab43 was significantly reduced in early-onset AD compared to late-onset AD (14.8 +/- 7.3 vs. 21.8 +/- 9.4 pg/ml, respectively), whereas the levels of Ab42 in the two AD groups were not significantly different (474.9 +/- 142.0 vs. 539.6 +/- 159.9 pg/ml, respectively). Ab43 and all core biomarkers were significantly altered in patients with AD compared to corresponding controls. NF-L was significantly increased in early-onset AD compared to younger controls, an effect not found between the older groups. Relationships between the A beta peptides and tau proteins, YKL-40, NF-L, GFAP and progranulin were also investigated without finding marked associations. However, age-associated increases in levels of tau proteins, YKL-40, NF-L and GFAP were found with respect to age in healthy controls. Results for these other analytes were similar to previously published data. A beta 43 did not improve diagnostic accuracy in either AD group compared to A beta 42. Discussion: Cerebrospinal fluid A beta 43, but not A beta 42 levels, varied significantly with age in patients with AD. If CSF levels of A beta peptides reflect amyloid deposition in brain, the possibility arises that there is a difference between A beta 43 and A beta 42 deposition in younger compared to older brain. However, the level of A beta 43 in CSF shows no improvement over A beta 42 regarding diagnostic accuracy.