Involvement of Perineuronal and Perisynaptic Extracellular Matrix in Alzheimer's Disease Neuropathology

Abstract

Brain extracellular matrix (ECM) is organized in specific patterns assumed to mirror local features of neuronal activity and synaptic plasticity. Aggrecan-based perineuronal nets (PNs) and brevican-based perisynaptic axonal coats (ACs) form major structural phenotypes of ECM contributing to the laminar characteristics of cortical areas. In Alzheimer’s disease (AD), the deposition of amyloid proteins and processes related to neurofibrillary degeneration may affect the integrity of the ECM scaffold. In this study we investigate ECM organization in primary sensory, secondary and associative areas of the temporal and occipital lobe. By detecting all major PN components we show that the distribution, structure and molecular properties of PNs remain unchanged in AD. Intact PNs occurred in close proximity to amyloid plaques and were even located within their territory. Counting of PNs revealed no significant alteration in AD. Moreover, neurofibrillary tangles never occurred in neurons associated with PNs. ACs were only lost in the core of amyloid plaques in parallel with the loss of synaptic profiles. In contrast, hyaluronan was enriched in the majority of plaques. We conclude that the loss of brevican is associated with the loss of synapses, whereas PNs and related matrix components resist disintegration and may protect neurons from degeneration.

Unique features of extracellular matrix in the mouse medial nucleus of trapezoid body – Implications for physiological functions

“…Since WFA and VVA preferentially detect oligosaccharide epitopes terminating in Nacetylgalactosamine (Tollefsen and Kornfeld, 1983b;Ha¨rtig et al, 1992;Giamanco et al, 2010;Morawski et al, 2011), a feature of chondroitin sulfate GAG chains, these lectins are thought to preferentially detect CSPGs in PNs. While often such labeling is used as a pars-pro-toto indication of PNs, we here aim at a differentiation of the subcompositon of the PNs.…”

Astrocytes and extracellular matrix in extrasynaptic volume transmission

“…The finding that ECM digestion increases performance in reversal learning without affecting already learned capacities brings forth the interesting challenge of guiding plastic changes using controlled ECM modulation [63]. On the other hand, mature PNNs and perisynaptic ACs create a protective shield attenuating the neurodegeneration evoked by neurotoxicity, oxidative stress or Ab deposits [14,15,65]. Aggrecan, cartilage link protein Crtl1 and tenascin-R have been identified as the main protective components of PNNs against iron-induced oxidative stress or Alzheimer's disease (AD) pathology [14,65].…”

“…On the other hand, mature PNNs and perisynaptic ACs create a protective shield attenuating the neurodegeneration evoked by neurotoxicity, oxidative stress or Ab deposits [14,15,65]. Aggrecan, cartilage link protein Crtl1 and tenascin-R have been identified as the main protective components of PNNs against iron-induced oxidative stress or Alzheimer's disease (AD) pathology [14,65]. The recent study of Lendvai et al [15] showed preserved ACs and increased brevican and Crtl1 expression in AD patients and transgenic APdE9 mice; this suggests an increased turnover of ECM molecules to maintain synaptic integrity.…”

Perineuronal nets and schizophrenia: The importance of neuronal coatings

“…Although their role is still not completely understood, PNNs have been implicated in ion homeostasis around highly active neurons (Bruckner et al, 1993; Bruckner et al, 1996a; Bruckner et al, 1996b; Hartig et al, 1999; Hartig et al, 2001; Hobohm et al, 1998) and neuroprotection (Bruckner et al, 1999; Cabungcal et al, 2013; Morawski et al, 2010; Morawski et al, 2012; Morawski et al, 2004; Schuppel et al, 2002). In addition, several studies have indicated that PNNs are important for memory and learning (Bruckner et al, 2000; Bukalo et al, 2001 Gogolla et al, 2009; Lee et al, 2012; Romberg et al, 2013; Saghatelyan et al, 2001).…”