Apolipoprotein L1 is increased in frontotemporal lobar degeneration postmortem brain tissue but not in cerebrospinal fluid. (December 2021)

• Record Type: Journal Article
• Authors: Hok‐A‐Hin, Yanaika S.; Dijkstra, Anke A.; Rabano, Alberto; Hoozemans, Jeroen J.; Castillo, Lucia; Pijnenburg, Yolande A.L.; Teunissen, Charlotte E.; Del Campo, Marta
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055154
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Frontotemporal Dementia (FTD) is a spectrum of heterogeneous disorders caused by frontal‐temporal lobar degeneration (FTLD). FTLD is characterized by brain protein aggregates of tau (FTLD‐Tau) or TDP43 (FTLD‐TDP) mainly. However, the clinicopathological heterogeneity across the FTLD spectrum makes ante‐mortem diagnosis of these FTLD pathological subtypes extremely challenging. Our recent proteomic analysis revealed apolipoprotein L1 (APOL1), involved in lipid metabolism and transport, as a potential cerebrospinal fluid (CSF) biomarker for FTLD. However, the association of APOL1 with the subtype of FTLD pathology is not known. Here, we aimed to characterize APOL1 expression in FTLD post‐mortem brain tissue with Tau or TDP pathology and validate its potential as a novel CSF biomarker for FTLD pathological subtypes. Method: APOL1 immunoreactivity was analyzed in paraffin‐embedded post‐mortem frontal cortex of 18 FTLD cases (FTLD‐Tau: 12 and FTLD‐TDP: 6) and 9 non‐demented controls. APOL1 levels were measured in post‐mortem frontal cortex (44 FTLD cases (FTLD‐Tau: 21 and FTLD‐TDP: 23) and 9 controls) and in ante‐mortem CSF (27 FTD patients (FTLD‐Tau: 12 and FTLD‐TDP: 15) and 15 controls) by western blot analysis and a validated in‐house APOL1 ELISA. APOL1 levels between groups were evaluated either by analysis of covariance (corrected for center) or Kruskal‐Wallis test. Result: Higher APOL1 immunoreactivity associated with neuronal and glia cells was observed in the frontal cortices of FTLD cases compared to controls (p<0.001, figure 1A). However, no differences were observed between the FTLD‐Tau and FTLD‐TDP subtypes. Western blot and ELISA analyses showed that APOL1 levels were increased in lysates from FTLD frontal cortex compared to controls (WB: p<0.001, figure 1B and ELISA: p<0.05, figure 1C), but were similar between the FTLD pathological subtypes. In CSF, we observed no changes in APOL1 between FTD patients and controls, nor between FTLD pathological subtypes. Conclusion: In this study, we were not able to validate APOL1 as a CSF biomarker for FTD using the current immunoassay. However, we do show a strong involvement of APOL1 in FTLD pathology irrespective of FTLD subtype. Future research should explore the specific role of APOL1 in the pathogenesis of FTLD.