Proteins Commonly Linked to Autism Spectrum Disorder and Alzheimer's Disease

Alexiou, Athanasios; Soursou, Georgia; Yarla, Nagendra Sastry; Ashraf, Ghulam Md

doi:10.2174/1389203718666170911145321

Cited by 15 publications

(7 citation statements)

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“…In addition, memory deficits, cognition changes, demyelination, oxidative stress, and inflammation have been reported to be an integral part of both ASD and Alzheimer's disease . Importantly, like in patients with Alzheimer's disease, a β‐amyloid overproduction or excessive deposition causing excessive activation of cortical neurons and neighboring glial cells has been described in patients with ASD . Also our children/teens presented with rates of NE, diurnal UI and FI which were higher as compared with those previously described, and presented with more continuous UI as compared to adults with the disease.…”

Section: Discussionsupporting

confidence: 60%

Bladder and bowel dysfunction, adaptive behaviour and psychiatric profiles in adults affected by autism spectrum disorders

Gubbiotti

Balboni

Bini

et al. 2019

Neurourology and Urodynamics

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Aims: Bladder and bowel dysfunction (BBD) have been recognized in children affected by autism spectrum disorder (ASD), but no consistent information exist in adults with the condition. We evaluated the prevalence of BBD and the impact of psychiatric and behavioural profiles in adults affected by ASD.Methods: Twenty-two adults and 13 children/teens with ASD and a matched group of typically developing subjects (TD) were prospectively studied. Patients and TD subjects underwent the evaluation of urinary incontinence (UI: diurnal, continuous or intermittent), nocturnal enuresis (NE), and bowel disturbances with the 3-day voiding and bowel diary. In addition, assessment of intellectual disability (ID) and psychiatric and adaptive behaviours with the Neuropsychiatric Inventory Scale (NPI) and the Vineland Adaptive Behaviour Scale 2ndEdition (Vineland-II), was performed. Results: In adults, any type of incontinence was observed in 81.8% of cases, and NE and intermittent UI in 59.0% and 36.3% of patients, respectively. Faecal incontinence and constipation were detected 36.3% and in 68.1% of cases, respectively. ID was severe in 2 cases and profound in 18; NPI and Vineland-II items most affected were "Irritability/Lability," "Motor Activity," and "Agitation," and IQ-Socialization and IQ-Communication. Significant relationships were identified between intermittent UI and greater ID (P < .02) and high "anxiety" (P < .05), and between NE and high "euphoria/elevated mood" (P < .05). These results were similar to those observed in children/teens. Conclusions:Adults with ASD, and greater ID and mood disorders, present with a high prevalence of BBD. A shared pathogenetic mechanism could underlie the co-occurrence of ASD, mood disorders, and BBD. K E Y W O R D Sadaptive behaviour, autism spectrum disorders, bladder and bowel dysfunction

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Section: Discussionsupporting

confidence: 60%

Bladder and bowel dysfunction, adaptive behaviour and psychiatric profiles in adults affected by autism spectrum disorders

Gubbiotti

Balboni

Bini

et al. 2019

Neurourology and Urodynamics

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“…Given the strong association of APP with AD and MDGA1 with late-onset AD ( 23 , 55 ), it is plausible that dysfunctions in the MDGA1–APP complex are linked to AD pathogenesis. However, accumulating evidence also points to a possible association of APP with autism spectrum disorders or schizophrenia ( 56 – 58 ) and the association of MDGA1 with schizophrenia ( 59 ). Future studies should systematically examine how the dysregulation of the MDGA1–APP complex elicits different manifestations during postnatal development.…”

Section: Discussionmentioning

confidence: 99%

MDGA1 negatively regulates amyloid precursor protein–mediated synapse inhibition in the hippocampus

Kim

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Balanced synaptic inhibition, controlled by multiple synaptic adhesion proteins, is critical for proper brain function. MDGA1 (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu [MAM] domain-containing glycosylphosphatidylinositol anchor protein 1) suppresses synaptic inhibition in mammalian neurons, yet the molecular mechanisms underlying MDGA1-mediated negative regulation of GABAergic synapses remain unresolved. Here, we show that the MDGA1 MAM domain directly interacts with the extension domain of amyloid precursor protein (APP). Strikingly, MDGA1-mediated synaptic disinhibition requires the MDGA1 MAM domain and is prominent at distal dendrites of hippocampal CA1 pyramidal neurons. Down-regulation of APP in presynaptic GABAergic interneurons specifically suppressed GABAergic, but not glutamatergic, synaptic transmission strength and inputs onto both the somatic and dendritic compartments of hippocampal CA1 pyramidal neurons. Moreover, APP deletion manifested differential effects in somatostatin- and parvalbumin-positive interneurons in the hippocampal CA1, resulting in distinct alterations in inhibitory synapse numbers, transmission, and excitability. The infusion of MDGA1 MAM protein mimicked postsynaptic MDGA1 gain-of-function phenotypes that involve the presence of presynaptic APP. The overexpression of MDGA1 wild type or MAM, but not MAM-deleted MDGA1, in the hippocampal CA1 impaired novel object-recognition memory in mice. Thus, our results establish unique roles of APP–MDGA1 complexes in hippocampal neural circuits, providing unprecedented insight into trans-synaptic mechanisms underlying differential tuning of neuronal compartment-specific synaptic inhibition.

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“…Alzheimer’s disease is a neurodegenerative disorder characterized by gradually progressive cognitive decline and functional impairment. Neuroinflammation may play a potential role in AD pathogenesis ( 73 , 74 ). However, the precise mechanism related to AD phenotype remains unclear.…”

Section: Crp and Admentioning

confidence: 99%

The Clinical Significance and Potential Role of C-Reactive Protein in Chronic Inflammatory and Neurodegenerative Diseases

2018

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C-reactive protein (CRP) is an acute-phase protein synthesized by hepatocytes in response to pro-inflammatory cytokines during inflammatory/infectious processes. CRP exists in conformationally distinct forms such as the native pentameric CRP and monomeric CRP (mCRP) and may bind to distinct receptors and lipid rafts and exhibit different functional properties. It is known as a biomarker of acute inflammation, but many large-scale prospective studies demonstrate that CRP is also known to be associated with chronic inflammation. This review is focused on discussing the clinical significance of CRP in chronic inflammatory and neurodegenerative diseases, such as cardiovascular disease, type 2 diabetes mellitus, age-related macular degeneration, hemorrhagic stroke, Alzheimer’s disease, and Parkinson’s disease, including recent advances on the implication of CRP and its forms specifically on the pathogenesis of these diseases. Overall, we highlight the advances in these areas that may be translated into promising measures for the diagnosis and treatment of inflammatory diseases.

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Proteins Commonly Linked to Autism Spectrum Disorder and Alzheimer's Disease

Cited by 15 publications

References 0 publications

Bladder and bowel dysfunction, adaptive behaviour and psychiatric profiles in adults affected by autism spectrum disorders

Bladder and bowel dysfunction, adaptive behaviour and psychiatric profiles in adults affected by autism spectrum disorders

MDGA1 negatively regulates amyloid precursor protein–mediated synapse inhibition in the hippocampus

The Clinical Significance and Potential Role of C-Reactive Protein in Chronic Inflammatory and Neurodegenerative Diseases

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