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Neurons associated with aggrecan-based perineuronal nets are protected against tau pathology in subcortical regions in Alzheimer's disease
Open accessAbstract
The biological basis for the selective vulnerability of neurons in Alzheimer's disease (AD) is elusive. Aggrecan-based perineuronal nets (PNs) of the extracellular matrix have been considered to contribute to neuroprotection in the cerebral cortex. In the present study, we investigated the organization of the aggrecan-based extracellular matrix in subcortical regions known to be preferentially affected by tau pathology in AD. Immunocytochemistry of aggrecan core protein was combined with detection of neurofibrillary degeneration. The results show that many regions affected by tau pathology in AD, such as the basal nucleus of Meynert, the dorsal thalamus, hypothalamic nuclei, raphe nuclei, and the locus coeruleus were devoid of a characteristic aggrecan-based extracellular matrix. Regions composed of nuclei with clearly different intensity of tau pathology, such as the amygdala, the thalamus and the oculomotor complex, showed largely complementary distribution patterns of neurofibrillary tangles and PNs. Quantification in the rostral interstitial nucleus of the longitudinal fascicle potentially affected by tau pathology in AD revealed that tau pathology was not accompanied by loss of aggrecan-based PNs. Neuro-fibrillary tangles in net-associated neurons extremely rarely occurred in the pontine reticular formation. We conclude that the low vulnerability of neurons ensheathed by PNs previously described for cortical areas in AD represents a more general phenomenon that also applies to subcortical regions. The aggrecan-based extracellular matrix of PNs may thus, be involved in neuroprotection.
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In the citing paper
“PNNs are reported to protect neurons against tau [37, 38] and Aβ pathology [39]”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [38]
In the citing paper
“Neurons that exhibit buildup of tau protein and neurofibrillary tangles are more likely to lack PNNs (Brückner et al., 1999; Morawski et al., 2010).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Morawski et al., 2010
In the citing paper
“a number of studies have shown alterations in PNNs and their constituents to be linked to various brain diseases, such as Alzheimer’s disease (Morawski et al., 2010, 2012; Kobayashi et al., 1989; Baig et al., 2005), epilepsy (McRae and Porter, 2012), multiple sclerosis (Gray et al., 2008), prion disease (Guentchev et al., 1999, Franklin et al., 2008) and stroke”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Morawski et al., 2010
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Metadata
- Authors
- Morawski, M., Brückner, G., Jäger, C., Seeger, G., & Arendt, T.
- Affiliations
- Leipzig University (DE)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 169
- Issue
- 3
- Pages
- 1347-1363
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2035362565
- Cited by
- 156
- References
- 96
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 12 · 2019: 5 · 2018: 18 · 2017: 8 · 2016: 6 · 2015: 8 · 2014: 13 · 2013: 5 · 2012: 6
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- German Research Foundation
- EU-Project “Neuropro” (223077)
- Universität Leipzig
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau pathology, neurofibrillary tangles, Alzheimer's disease, subcortical structures, neuroprotection, extracellular matrix, nucleus basalis of Meynert, dorsal thalamus, hypothalamic nuclei, raphe nuclei, locus coeruleus, pontine reticular formation, amygdala
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Extracellular Matrix, Female, Humans, Male, Middle Aged, Neurons, Organ Specificity, Neurofibrillary Tangles, tau Proteins, Aggrecans
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