DIFFERENT PATHOLOGICAL DISTRIBUTION PATTERN OF PHOSPHORYLATED TAU AND MICROGLIA IN AMNESTIC AND NON-AMNESTIC ALZHEIMER’S DISEASE

Abstract

The classical distribution pattern for neurofibrillary tangles (NFT) is not seen in all Alzheimer’s disease (AD) patients (Murray, 2011). Of all patients, 6-14% presents with non-amnestic symptoms such as language and visuospatial dysfunction (Dubois, 2014). There is an association between non-amnestic symptoms and the severity of NFT pathology in the parietal cortex (Tang Wai, 2004). We hypothesize that next to NFT the occurrence of phosphorylated tau, amyloid beta and microglia differ in cortical distribution between amnestic (AAD) and non-amnestic AD (NAAD) patients. AAD cases (n=10; mean age=85) were defined as having memory dysfunction as presenting symptom and a NFT distribution typical according to Braak staging. NAAD cases (n=10; mean age=63) were defined as having non-amnestic symptomatology as presenting symptom and a predominance of NFT in the parietal cortex compared with the temporal cortex. In the temporal and parietal cortex the presence of amyloid (A)beta (n-terminus), phosphorylated (p)Tau (pSer202+Thr205), and microglia (HLA-DP, DQ, DR) was assessed by immunohistochemistry and analyzed for optical density using the ImageJ analysis programme. In NAAD cases levels of pTau were similar in the parietal and temporal cortex, while AAD cases showed 20% higher level of pTau in the temporal cortex. Compared with the AAD cases, NAAD cases had 15% higher levels of pTau in the parietal cortex (p<0.05). Remarkably, no differences in Abeta levels were found, neither between groups nor regions. In the parietal cortex, the NAAD group had twice the amount of microglia compared with their temporal cortex, whereas the AAD group had twice the amount of microglia in their temporal cortex. The NAAD group had a three times higher load of microglia in the parietal cortex than the AAD group (p<0.05). pTau and microglia levels did not differ in the temporal cortex between groups. Our data are in line with previous findings illustrating different distribution patterns of pathological hallmarks in variants of AD. The increased presence of pTau and microglia in the parietal cortex of NAAD compared with AAD suggests a different underlying neuropathological mechanism and disease progression in AD variants. The mean phosphorylated tau (AT8), amyloid beta (Abeta), and microglia (CR3/43) immunoreactivity per region in amnestic and non-amnestic Alzheimer's disease (AD) cases. + = significant region effect * = significant region per group effect