P4‐226: Quantification of Tau Oligomers From Mouse Brain Tissue

Abstract

Background: Obstructive sleep apnea syndrome (OSAS) occurs more frequently in Alzheimers disease (AD) than in controls. OSAS is characterized by the obstruction of the upper airway resulting in nocturnal intermittent hypoxia. Hypoxia has been found to be related to the Alzheimer biomarkers amyloid-beta and tau in animal studies. The aim of the present study was to investigate whether a history of OSAS is associated with cerebrospinal fluid (CSF) levels of amyloid-beta 42 (AB42), total tau (tau) and phosphorylated tau (ptau) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD. Methods: We included 59 patients who reported OSAS in their medical history (age 63 (8) years, 11 (19%) female; 14 AD, 15 MCI, 30 SCD) from the Amsterdam Dementia Cohort. We matched these patients for baseline diagnosis, gender, age, and year of evaluation, on a 1:2 basis to patients without an OSAS history (N¼118). CSF AB42, tau and ptau were assessed using ELISA (Innotest). We assessed the association between OSAS and the CSF biomarkers with Linear Mixed Models (LMM), that included terms for OSAS, diagnosis, and the interactions between OSAS and diagnosis. All models were adjusted for APOE E4 status. Results:In the total sample there was no association between OSAS and CSF biomarkers. The relationship between OSAS and tau tended to be different between diagnostic groups (p-value interaction .095). Post-hoc analysis showed that AD patients with a history of OSAS had higher tau levels than those without OSAS (estimated mean [95% CI]: 845 vs. 647 [549-744] pg/ml, p-value ¼ .02). OSAS was not associated with tau in SCD and MCI patients. There was no interaction between OSAS and diagnosis for CSF AB42 and ptau. Conclusions: We found that a history of OSAS is associated with higher CSF tau levels in AD. These findings could fit with the idea that hypoxia might have an additive effect to neuronal injury in AD, or vice versa, that patients with high tau levels are at increased risk of OSAS. However, inferences on causal relationships cannot be made given the observational nature of the study.Background: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases of the world. One of its major hallmarks is the hyperphosphorylation of tau protein leading to intracellular neurofibrillary tangles (NFTs) in neurons. These tangles represent an end stage of paired helical filament (PHF) aggregation, which are found in neuropil threads in early stages of dementia. The hyperphosphorylation occurs at different tau protein residues like serine, threonine and tyrosine, including several phospho-sites especially related to AD. However, appearance, quantity and location of NFTs are still not fully understood. Methods: Using indirect immunofluorescence and quantitative image analysis, tau pathologies in diseased and healthy human brain, as well as transgenic and non-transgenic APP SL mice were investigated. We analyzed three different phospho-sites (pSer199, pSer396 and pSer422) in cortical regions and ...