Glycosaminoglycans in Cortical Autopsy Samples from Alzheimer Brain

Jenkins, Huw G.; Bachelard, H. S.

doi:10.1111/j.1471-4159.1988.tb01135.x

Cited by 35 publications

(17 citation statements)

References 27 publications

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“…However, in contrast to persisting levels of ECM proteins and hyaluronan in PNs, hyaluronan is enriched in the coronal and marginal zones of the amyloid plaques. This is in concordance with biochemical investigations showing an increase of hyaluronan up to 26% in the temporal lobe of AD patients (50). The focal elevation of hyaluronan concentration may be related to reactive astrocytes in the surrounding tissue, as the hyaluronan receptor CD44 is located at radially oriented astrocytic processes massively penetrating these plaque territories (3).…”

Section: Discussionsupporting

confidence: 86%

“…Despite advanced stages of amyloid and tau pathology, PNs and ACs, two widely distributed structural phenotypes of condensed ECM were virtually unchanged. This is in agreement with our previous work in human APP transgenic Tg2576 mice showing advanced cortical amyloid plaque pathology (69) and with biochemical data (50).…”

Section: Area-specific Laminar Distribution Patterns Of Pns and Perissupporting

confidence: 93%

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

Morawski¹,

Brückner²,

Jäger³

et al. 2012

Brain Pathology

133

111

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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.

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Section: Discussionsupporting

confidence: 86%

Section: Area-specific Laminar Distribution Patterns Of Pns and Perissupporting

confidence: 93%

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

Morawski¹,

Brückner²,

Jäger³

et al. 2012

Brain Pathology

133

111

View full text Add to dashboard Cite

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“…Another candidate for the endogenous ligand that activates TLR4 in neurons in response to Aβ or HNE mediated toxic conditions is hyaluronan fragments. Levels of hyaluronate were reported to be increased in the temporal cortex of AD patients compared to age-matched control subjects (Jenkins and Bachelard, 1988). Hyaluronases are activated in injured neural tissue resulting in the generation of hyaluronan fragments (Al 'Qteishat et al, 2006) that have been reported capable of activating TLR2 and TLR4 in immune cells (Termeer et al, 2002;Jiang et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid β-peptide and the membrane lipid peroxidation product 4-hydroxynonenal

Tang¹,

Lathia²,

Selvaraj³

et al. 2008

Experimental Neurology

225

167

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The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We recently found that neurons express several TLRs, and that the levels of TLR2 and TLR4 are increased in neurons in response to energy deprivation. Here we report that TLR4 expression increases in neurons when exposed to amyloid β-peptide (Aβ1-42) or the lipid peroxidation product 4-hydroxynonenal (HNE). Neuronal apoptosis triggered by Aβ and HNE was mediated by jun N-terminal kinase (JNK); neurons from TLR4 mutant mice exhibited reduced JNK and caspase-3 activation and were protected against apoptosis induced by Aβ and HNE. Levels of TLR4 were decreased in inferior parietal cortex tissue specimens from end-stage AD patients compared to aged-matched control subjects, possibly as the result of loss of neurons expressing TLR4. Our findings suggest that TLR4 signaling increases the vulnerability of neurons to Aβ and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for AD.

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“…One study utilizing electrophoretic separation of glycosaminoglycans indicated a moderate increase in HA concentration in 30 month-old rat brain tissue compared to tissues from younger animals (Jenkins and Bachelard, 1988a). HA is similarly elevated in brains from patients with Alzheimer’s disease (Jenkins and Bachelard, 1988b; Suzuki et al, 1965). Whether HA similarly accumulates in the primate brain with normative aging has not been previously investigated.…”

Section: Introductionmentioning

confidence: 99%

Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan

Cargill

Kohama

Struve

et al. 2012

Neurobiology of Aging

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The glycosaminoglycan hyaluronan (HA) accumulates in central nervous system lesions where it limits astrogliosis but also inhibits oligodendrocyte progenitor cell (OPC) maturation. The role of hyaluronan in normative brain aging has not been previously investigated. Here, we tested the hypothesis that HA accumulates in the aging non-human primate brain. We found that HA levels significantly increase with age in the gray matter of rhesus macaques. HA accumulation was linked to age-related increases in the transcription of HA Synthase-1 (HAS1) expressed by reactive astrocytes but not changes in the expression of other HAS genes or hyaluronidases. HA accumulation was accompanied by increased expression of CD44, a transmembrane HA receptor. Areas of gray matter with elevated HA in older animals demonstrated increased numbers of olig2+ OPCs, consistent with the notion that HA may influence OPC expansion or maturation. Collectively, these data indicate that HAS1 and CD44 are transcriptionally upregulated in astrocytes during normative aging and are linked to HA accumulation in gray matter.

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Glycosaminoglycans in Cortical Autopsy Samples from Alzheimer Brain

Cited by 35 publications

References 27 publications

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

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

Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid β-peptide and the membrane lipid peroxidation product 4-hydroxynonenal

Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan

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