Neuroinflammation in posterior cortical atrophy and typical Alzheimer’s disease

Abstract

AbstractBackgroundPosterior cortical atrophy (PCA) is a neurodegenerative, predominantly young‐onset syndrome most commonly caused by Alzheimer’s disease (AD). PCA presents with visual and spatial dysfunction attributed to occipito‐parietal or “posterior” brain regions rather than memory difficulties characteristic of typical Alzheimer’s disease (tAD) attributed to medial temporal regions. Whilst the underlying pathology of PCA and tAD are usually the same: Aβ plaques and tau neurofibrillary tangles (NFTs), imaging and neuropathological work points to a more posterior distribution of NFTs in PCA. Differences in inflammatory response have been proposed to relate to AD heterogeneity evident in PCA. This study compared neuroinflammation between PCA and tAD in relation to Aβ and tau at autopsy.MethodImmunohistochemistry for microglial markers (CD68, Iba1, HLA‐DR/DP/DQ) and Aβ/tau was carried out on the frontal, parietal, temporal and occipital brain regions of 26 clinically and pathologically phenotyped PCA cases and 27 age and gender‐matched tAD cases from UCL Queen Square Brain Bank. All PCA patients had a neuropathological diagnosis of AD (Table 1). Marker load was quantified as percentage surface area of the 4 brain regions using Image J software.ResultThis study showed significantly lower temporal CD68 load in the tAD compared with the PCA group, (reduced CD68% area: ‐ 0.88%; (95%CI [‐0.42,‐1.34]), p<0.001). Frontal CD68 load was significantly lower in PCA compared with tAD, (reduced CD68% area: ‐0.54; (95%CI[‐1.01,‐0.07]), p = 0.025), see Fig 1A. Parietal tau was significantly higher in the PCA group compared with the tAD group (increased tau % area: 5.15%; (95% CI [0.55, 9.76]), p = 0.029. The highest observed tau load within the PCA group was in the frontal region and for tAD in the temporal region, see Fig 1B.ConclusionRegional increases in tau and decreases in markers of activated microglia differ between PCA and tAD. Discrepancies between tau and activated microglial markers are particularly apparent in temporal and frontal regions in tAD and PCA respectively. This may be in line with the notion of a disconnect between microglial phagocytic activity at later stages of Alzheimer’s disease leading to further accumulation of tau and subsequent neuronal death.