BACKGROUND: There is initial evidence suggesting that biomarker neurogranin (Ng) may distinguish Alzheimer's disease (AD) from other neurodegenerative diseases. Therefore, we assessed (a) the discriminant ability of cerebrospinal fluid (CSF) Ng levels to distinguish between AD and frontotemporal lobar degeneration (FTLD) pathology and between different stages within the same disease, (b) the relationship between Ng levels and cognitive performance in both AD and FTLD pathology, and (c) whether CSF Ng levels vary by apolipoprotein E (APOE) polymorphism in the AD continuum. METHODS: Participants with subjective cognitive decline (SCD) (n = 33), amnestic mild cognitive impairment (aMCI) due to AD (n = 109), AD dementia (n = 67), MCI due to FTLD (n = 25), and FTLD dementia (n = 29) were recruited from the Czech Brain Aging Study. One-way analysis of covariance (ANCOVA) assessed Ng levels in diagnostic subgroups. Linear regressions evaluated the relationship between CSF Ng levels, memory scores, and APOE polymorphism. RESULTS: Ng levels were higher in aMCI-AD patients compared to MCI-FTLD (F[1, 134] = 15.16, p < .001), and in AD-dementia compared to FTLD-dementia (F[1, 96] = 4.60, p = .029). Additionally, Ng levels were higher in FTLD-dementia patients compared to MCI-FTLD (F[1, 54]= 4.35, p = .034), lower in SCD participants compared to aMCI-AD (F[1, 142] = 10.72, p = .001) and AD-dementia (F[1, 100] = 20.90, p < .001), and did not differ between SCD participants and MCI-FTLD (F[1, 58]= 1.02, p = .491) or FTLD-dementia (F[1, 62]= 2.27, p = .051). The main effect of diagnosis across the diagnostic subgroups on Aβ1-42/Ng ratio was significant too (F[4, 263]=, p < .001). We found a non-significant association between Ng levels and memory scores overall (β=-0.25, p = .154) or in AD diagnostic subgroups, and non-significant differences in this association between overall AD APOE ε4 carriers and non-carriers (β=-0.32, p = .358). CONCLUSIONS: In this first study to-date to assess MCI and dementia due to AD or FTLD within one study, elevated CSF Ng appears to be an early biomarker of AD-related impairment, but its role as a biomarker appears to diminish after dementia diagnosis, whereby dementia-related underlying processes in AD and FTLD may begin to merge. The Aβ1-42/Ng ratio discriminated AD from FTLD patients better than Ng alone. CSF Ng levels were not related to memory in AD or FTLD, suggesting that Ng may be a marker of the biological signs of disease state rather than cognitive deficits.

• Klíčová slova
• APOE, Alzheimer’s disease, Frontotemporal lobar degeneration, Memory, Neurogranin,
• MeSH
• Alzheimerova nemoc * mozkomíšní mok   diagnóza   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoproteiny E genetika   mozkomíšní mok   MeSH
• biologické markery * mozkomíšní mok   MeSH
• frontotemporální lobární degenerace * mozkomíšní mok   diagnóza   MeSH
• kognitivní dysfunkce * mozkomíšní mok   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurogranin * mozkomíšní mok   MeSH
• neuropsychologické testy MeSH
• průřezové studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• apolipoproteiny E MeSH
• biologické markery * MeSH
• neurogranin * MeSH
• NRGN protein, human MeSH Prohlížeč