The Impact of Apolipoprotein E Allelic Variants on Alzheimer’s Disease

Serrano, Ezequiel; Sanz, Pablo; Barrantes, Francisco J.

doi:10.1007/978-3-030-61721-9_29

Cited by 2 publications

(3 citation statements)

References 220 publications

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“…ApoE in its various isoforms E2, E3, and E4, coded by the gene alleles ε2, ε3, and ε4, are a family of apolipoproteins also present in the CNS; the brain is the organ with the second-highest ApoE expression after the liver (Linton et al, 1991;Serrano et al, 2021). The ApoE isoforms differ from each other in only one amino acid residue.…”

Section: Apolipoproteins and Asdmentioning

confidence: 99%

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Dysregulation of Neuronal Nicotinic Acetylcholine Receptor–Cholesterol Crosstalk in Autism Spectrum Disorder

Vallés

Barrantes

2021

Front. Mol. Neurosci.

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Autism spectrum disorder (ASD) is a set of complex neurodevelopmental diseases that include impaired social interaction, delayed and disordered language, repetitive or stereotypic behavior, restricted range of interests, and altered sensory processing. The underlying causes of the core symptoms remain unclear, as are the factors that trigger their onset. Given the complexity and heterogeneity of the clinical phenotypes, a constellation of genetic, epigenetic, environmental, and immunological factors may be involved. The lack of appropriate biomarkers for the evaluation of neurodevelopmental disorders makes it difficult to assess the contribution of early alterations in neurochemical processes and neuroanatomical and neurodevelopmental factors to ASD. Abnormalities in the cholinergic system in various regions of the brain and cerebellum are observed in ASD, and recently altered cholesterol metabolism has been implicated at the initial stages of the disease. Given the multiple effects of the neutral lipid cholesterol on the paradigm rapid ligand-gated ion channel, the nicotinic acetylcholine receptor, we explore in this review the possibility that the dysregulation of nicotinic receptor-cholesterol crosstalk plays a role in some of the neurological alterations observed in ASD.

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Section: Apolipoproteins and Asdmentioning

confidence: 99%

“…ApoE has a myriad of functions in the CNS, participating in lipid transport and metabolism, growth, maintenance, and repair of axons and myelin during neuronal development (see recent review in ref. Serrano et al, 2021). The major function of ApoE is its participation in cholesterol homeostasis, which is unique in the brain.…”

Section: Apolipoproteins and Asdmentioning

confidence: 99%

Dysregulation of Neuronal Nicotinic Acetylcholine Receptor–Cholesterol Crosstalk in Autism Spectrum Disorder

Vallés

Barrantes

2021

Front. Mol. Neurosci.

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“…The strongest genetic risk factor for AD is the presence of the apolipoprotein E (ApoE) allele epsilon 4 ( APOE4 ), which is present in roughly 50% of all cases, albeit with important ethnic variability [ 215 ]. ApoE4 is involved in lipid metabolism, most importantly in cholesterol transport, and cholesterol dyslipidemias are thought to be involved in AD pathogenesis [ 216 ].…”

Section: Interventions Targeting Neuroplasticity In Animal Models Of Admentioning

confidence: 99%

Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease

Colavitta,

Barrantes

2023

Pharmaceutics

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Alzheimer disease (AD) is the most prevalent form of dementia among elderly people. Owing to its varied and multicausal etiopathology, intervention strategies have been highly diverse. Despite ongoing advances in the field, efficient therapies to mitigate AD symptoms or delay their progression are still of limited scope. Neuroplasticity, in broad terms the ability of the brain to modify its structure in response to external stimulation or damage, has received growing attention as a possible therapeutic target, since the disruption of plastic mechanisms in the brain appear to correlate with various forms of cognitive impairment present in AD patients. Several pre-clinical and clinical studies have attempted to enhance neuroplasticity via different mechanisms, for example, regulating glucose or lipid metabolism, targeting the activity of neurotransmitter systems, or addressing neuroinflammation. In this review, we first describe several structural and functional aspects of neuroplasticity. We then focus on the current status of pharmacological approaches to AD stemming from clinical trials targeting neuroplastic mechanisms in AD patients. This is followed by an analysis of analogous pharmacological interventions in animal models, according to their mechanisms of action.

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The Impact of Apolipoprotein E Allelic Variants on Alzheimer’s Disease

Cited by 2 publications

References 220 publications

Dysregulation of Neuronal Nicotinic Acetylcholine Receptor–Cholesterol Crosstalk in Autism Spectrum Disorder

Dysregulation of Neuronal Nicotinic Acetylcholine Receptor–Cholesterol Crosstalk in Autism Spectrum Disorder

Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease

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