Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

Porcelli, Stefano; Calabrò, Marco; Crisafulli, Concetta; Politis, Antonis; Liappas, Ioannis; Albani, Diego; Forloni, Gianluigi; Benedetti, Francesco; Papadimitriou, George N.; Serretti, Alessandro

doi:10.1159/000497164

Cited by 10 publications

(5 citation statements)

References 53 publications

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“…The study found that the rs4680 variant of the COMT genotype was associated with AD, and the rs174696 variant of COMT was associated with depression in Greek AD patients. Thus, the study supported the role of the rs4680 variant in the disease pathogenesis of AD [ 29 ]. Since this research was conducted on a Greek and Italian subsample, this work should be replicated among other population samples as well.…”

Section: Reviewsupporting

confidence: 71%

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

Srivastava¹,

Ochuba²,

Sandhu³

et al. 2021

Cureus

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Different polymorphisms of the catechol-O-methyltransferase (COMT) gene affect the COMT enzyme activity. The COMT enzyme plays a major role in the pathophysiology of various neurological and psychiatric disorders. This review article aims to discuss what recent research has discovered about the association of COMT genotype polymorphism with neurological and psychiatric disorders and the scope for the knowledge to be applied for advancement in therapeutics. We searched PubMed and Google Scholar databases and found 1656 articles. We included observational studies, clinical trials, and meta-analyses in the English language published between 2019 and 2021. We screened the articles based on the title and the abstract and found 26 relevant articles. Diseases or conditions studied primarily were schizophrenia, Parkinson's disease, Alzheimer's disease, substance use, and depression. This article highlights how genetics influences the susceptibility of an individual to neurological and psychiatric diseases and the variations in the specific symptoms of those diseases. The review showed that the variability in individual response to therapeutic interventions stems from the gene level. This knowledge can contribute towards the dawn of a new era of personalized medicine.

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Section: Reviewsupporting

confidence: 71%

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

Srivastava¹,

Ochuba²,

Sandhu³

et al. 2021

Cureus

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“…Molecules like Programmed Cell Death 5 (PDCD5) may play a role in programmed cell death observed in neurodegenerative disorders [ 111 ]. Genomic mutations in Sorbin and SH3 Domain Containing 3 (SORBS3) that may regulate cell proliferation were associated with Alzheimer’s disease [ 112 , 113 ]. Thymus, Brain And Testes Associated (TBATA) that plays a role in neurite outgrowth increased in the circulation in AD [ 114 ].…”

Section: Discussionmentioning

confidence: 99%

The plasma peptides of Alzheimer’s disease

Florentinus-Mefailoski

Bowden

Scheltens

et al. 2021

Clin Proteom

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Background A practical strategy to discover proteins specific to Alzheimer’s dementia (AD) may be to compare the plasma peptides and proteins from patients with dementia to normal controls and patients with neurological conditions like multiple sclerosis or other diseases. The aim was a proof of principle for a method to discover proteins and/or peptides of plasma that show greater observation frequency and/or precursor intensity in AD. The endogenous tryptic peptides of Alzheimer’s were compared to normals, multiple sclerosis, ovarian cancer, breast cancer, female normal, sepsis, ICU Control, heart attack, along with their institution-matched controls, and normal samples collected directly onto ice. Methods Endogenous tryptic peptides were extracted from blinded, individual AD and control EDTA plasma samples in a step gradient of acetonitrile for random and independent sampling by LC–ESI–MS/MS with a set of robust and sensitive linear quadrupole ion traps. The MS/MS spectra were fit to fully tryptic peptides within proteins identified using the X!TANDEM algorithm. Observation frequency of the identified proteins was counted using SEQUEST algorithm. The proteins with apparently increased observation frequency in AD versus AD Control were revealed graphically and subsequently tested by Chi Square analysis. The proteins specific to AD plasma by Chi Square with FDR correction were analyzed by the STRING algorithm. The average protein or peptide log10 precursor intensity was compared across disease and control treatments by ANOVA in the R statistical system. Results Peptides and/or phosphopeptides of common plasma proteins such as complement C2, C7, and C1QBP among others showed increased observation frequency by Chi Square and/or precursor intensity in AD. Cellular gene symbols with large Chi Square values (χ2 ≥ 25, p ≤ 0.001) from tryptic peptides included KIF12, DISC1, OR8B12, ZC3H12A, TNF, TBC1D8B, GALNT3, EME2, CD1B, BAG1, CPSF2, MMP15, DNAJC2, PHACTR4, OR8B3, GCK, EXOSC7, HMGA1 and NT5C3A among others. Similarly, increased frequency of tryptic phosphopeptides were observed from MOK, SMIM19, NXNL1, SLC24A2, Nbla10317, AHRR, C10orf90, MAEA, SRSF8, TBATA, TNIK, UBE2G1, PDE4C, PCGF2, KIR3DP1, TJP2, CPNE8, and NGF amongst others. STRING analysis showed an increase in cytoplasmic proteins and proteins associated with alternate splicing, exocytosis of luminal proteins, and proteins involved in the regulation of the cell cycle, mitochondrial functions or metabolism and apoptosis. Increases in mean precursor intensity of peptides from common plasma proteins such as DISC1, EXOSC5, UBE2G1, SMIM19, NXNL1, PANO, EIF4G1, KIR3DP1, MED25, MGRN1, OR8B3, MGC24039, POLR1A, SYTL4, RNF111, IREB2, ANKMY2, SGKL, SLC25A5, CHMP3 among others were associated with AD. Tryptic peptides from the highly conserved C-terminus of DISC1 within the sequence MPGGGPQGAPAAAGGGGVSHRAGSRDCLPPAACFR and ARQCGLDSR showed a higher frequency and highest intensity in AD compared to all other disease and controls. Conclusion Proteins apparently expressed in the brain that were directly related to Alzheimer’s including Nerve Growth Factor (NFG), Sphingomyelin Phosphodiesterase, Disrupted in Schizophrenia 1 (DISC1), the cell death regulator retinitis pigmentosa (NXNl1) that governs the loss of nerve cells in the retina and the cell death regulator ZC3H12A showed much higher observation frequency in AD plasma vs the matched control. There was a striking agreement between the proteins known to be mutated or dis-regulated in the brains of AD patients with the proteins observed in the plasma of AD patients from endogenous peptides including NBN, BAG1, NOX1, PDCD5, SGK3, UBE2G1, SMPD3 neuronal proteins associated with synapse function such as KSYTL4, VTI1B and brain specific proteins such as TBATA.

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“…It appears vital to also acknowledge “choosing to be distant” as having implications for an agency in people living with dementia. Withdrawal from social interaction may be a consequence of the disease process ( Porcelli et al, 2019 ), but it may also be perceived as a choice even in people with more advanced dementia ( Ciofi et al, 2022 ). It appeared here that some people actively choose not to join in with group activities: physically distancing themselves from surrounding social activity, describing making a choice on when to “join in.” Without more closely investigating the intent of a person with dementia, we may ascribe their apparently more limited actions to apathy; a dementia symptom rather than their active choice.…”

Section: Discussionmentioning

confidence: 99%

“The Dynamic Nature of Being a Person”: An Ethnographic Study of People Living With Dementia in Their Communities

et al. 2023

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Background and Objectives A dementia diagnosis can impact on social interactions. This study aims to understand how people living with dementia act as social beings within everyday interactions in their local communities. Research Design and Methods Focused ethnography informed by Spradley’s approach to data collection and analysis. Observations in community spaces. Results Twenty-nine observations were undertaken in everyday social settings with 11 people with dementia who were part of a longitudinal interview study. Data consisted of 40 hours of observation, and researcher fieldnotes. The overarching theme ‘The dynamic nature of being a person’ encapsulates participants’ exhibited experiences in negotiating to attain and sustain an acknowledged place in their communities. Two sub-themes characterized contexts and actions: 1 ‘Being me - not dementia’: participants constructed narratives to assert their ontological presence in social settings. They and others used strategies to mediate cognitive changes evidencing dementia. 2 ‘Resisting or acquiescing to ‘being absent in place’’: Participants were often able to resist being absent to the gaze of others, but some social structures and behaviors led to a person being ‘in place’, yet not having their presence confirmed. Discussion and Implications People living with dementia can actively draw on personal attributes, familiar rituals, objects, and social roles to continue to present themselves as social beings. Identifying how post-diagnosis people may self-manage cognitive changes to retain their presence as a person can help health and social care practitioners and families collaborate with the person living with dementia enabling them to have a continued social presence.

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Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

Cited by 10 publications

References 53 publications

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

The plasma peptides of Alzheimer’s disease

“The Dynamic Nature of Being a Person”: An Ethnographic Study of People Living With Dementia in Their Communities

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