Your search for: 'author:("Jayadev, Suman")' has returned 8 results. (0.012s) Save search

Authors: Jiang, Haowei | Jayadev, Suman | Lardelli, Michael | Newman, Morgan

Article Type: Review Article

Abstract: PRESENILIN 1 (PSEN1 ) and PRESENILIN 2 (PSEN2 ) genes are loci for mutations causing familial Alzheimer’s disease (fAD). However, the function of these genes and how they contribute to fAD pathogenesis has not been fully determined. This review provides a summary of the overlapping and independent functions of the PRESENILINS with a focus on the lesser studied PSEN2 . As a core component of the γ-secretase complex, the PSEN2 protein is involved in many γ-secretase-related physiological activities, including innate immunity, Notch signaling, autophagy, and mitochondrial function. These physiological activities have all been associated with AD progression, indicating that PSEN2 …plays a particular role in AD pathogenesis. Show more

Keywords: Alzheimer’s disease, γ-secretase, PRESENILIN 1, PRESENILIN 2

DOI: 10.3233/JAD-180656

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1323-1339, 2018

Authors: Davis, Marie Y. | Keene, C. Dirk | Jayadev, Suman | Bird, Thomas

Article Type: Research Article

Abstract: Background: Dementia is a common feature in both Huntington's disease (HD) and Alzheimer's disease (AD), as well as in the general elderly population. Few studies have examined elderly HD patients with dementia for neuropathologic evidence of both HD and AD. Objective: We present neuropathological findings in a retrospective case series of 15 elderly HD patients (ages 60–91 years), 11 of whom had prominent clinical dementia. Methods: Post-mortem brain tissue was examined and stained for evidence of both HD and AD including Vonsattel grading and Htt-repeat expansion, Bielskowsky, tau, β amyloid, and TDP43 immunostaining. Results: Mean age at death was 76.8 …years, mean disease duration was 18.6 years, and mean CAG repeat expansion was 42. Evidence of AD in addition to HD pathology was present in 9 of 11 (82%) patients with prominent dementia, suggesting that AD may be more commonly co-occurring with HD than previously appreciated. Two patients had only HD as the basis of dementia and four patients did not have prominent dementia. One patient with marked parkinsonian features was not L-dopa responsive and had no substantia nigra Lewy bodies at autopsy. Conclusions: Our study suggests that AD may frequently contribute to cognitive decline in elderly HD patients which complicates the assessment and management of such individuals. Further study is needed to determine if there is a higher incidence of AD in persons with HD compared to the general population. In addition, our series includes one HD patient whose clinical features masqueraded as Parkinson's disease but was not responsive to levodopa therapy. Show more

Keywords: Huntington's disease, Alzheimer's disease, dementia, parkinsonism

DOI: 10.3233/JHD-140111

Citation: Journal of Huntington's Disease, vol. 3, no. 2, pp. 209-217, 2014

Authors: Tsuang, Debby W. | Greenwood, Tiffany A. | Jayadev, Suman | Davis, Marie | Shutes-David, Andrew | Bird, Thomas D.

Article Type: Research Article

Abstract: Background: Psychotic symptoms of delusions and hallucinations occur in about 5% of persons with Huntington’s disease (HD). The mechanisms underlying these occurrences are unknown, but the same symptoms also occur in schizophrenia, and thus genetic risk factors for schizophrenia may be relevant to the development of psychosis in HD. Objective: To investigate the possible role of genes associated with schizophrenia in the occurrence of psychotic symptoms in HD. Methods: DNA from subjects with HD and psychosis (HD+P; n  = 47), subjects with HD and no psychosis (HD-P; n  = 126), and controls (CTLs; n  = 207) was genotyped using the Infinium PsychArray-24 v1.1 …BeadChip. The allele frequencies of single-nucleotide polymorphisms (SNPs) that were previously associated with schizophrenia and related psychiatric disorders were compared between these groups. Results: Of the 30 candidate genes tested, 10 showed an association with psychosis in HD. The majority of these genes, including CTNNA2 , DRD2 , ERBB4 , GRID2 , GRIK4 , GRM1 , NRG1 , PCNT , RELN , and SLC1A2 , demonstrate network interactions related to glutamate signaling. Conclusions: This study suggests genetic associations between several previously identified candidate genes for schizophrenia and the occurrence of psychotic symptoms in HD. These data support the potential role of genes related to glutamate signaling in HD psychosis. Show more

Keywords: Delusions, genetic association studies, genetic predisposition to disease, genetics, glutamates, hallucinations, Huntington disease, modifier genes, psychotic disorders, schizophrenia

DOI: 10.3233/JHD-170277

Citation: Journal of Huntington's Disease, vol. 7, no. 1, pp. 51-59, 2018

Authors: Clute-Reinig, Nicholas | Jayadev, Suman | Rhoads, Kristoffer | Le Ny, Anne-Laure

Article Type: Article Commentary

Abstract: Dementia and Alzheimer’s disease (AD) are global health crises, with most affected individuals living in low- or middle-income countries. While research into diagnostics and therapeutics remains focused exclusively on high-income populations, recent technological breakthroughs suggest that low-cost AD diagnostics may soon be possible. However, as this disease shifts onto those with the least financial and structural ability to shoulder its burden, it is incumbent on high-income countries to develop accessible AD healthcare. We argue that there is a scientific and ethical mandate to develop low-cost diagnostics that will not only benefit patients in low-and middle-income countries but the AD field …as a whole. Show more

Keywords: Alzheimer’s disease diagnostics, dementia, developing countries, global health, health equity, healthcare disparities, neurological diagnostic techniques

DOI: 10.3233/JAD-210663

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1453-1455, 2021

Authors: Davis, Marie | Wheelock, Vicki | Talman, Lauren | Latimer, Caitlin | Vicars, Brenda | Lin, Anny | Jayadev, Suman | Bird, Thomas

Article Type: Research Article

Abstract: Background: Persons with Huntington’s disease (HD) are at increased risk for subdural hematomas (SDH) because of underlying brain atrophy and increased frequency of falls and head trauma. SDH can cause serious disability, but there is little information about the association of SDH with HD in the medical literature. Objective: To review the occurrence and characteristics of SDH seen in clinics specializing in HD. Methods: A retrospective review identifying the occurrence and manifestations of SDH in HD patients attending three HDSA Centers of Excellence. Results: Twenty-five HD patients (16F/9M) were identified with SDH. Twelve (44%) SDH were bilateral, 16 (60%) required …surgical intervention, and 2 resulted in death. Mean age at the time of SDH was 60 years, mean duration of HD symptoms prior to event was 8 years, mean CAG repeat expansion size was 43 and mean UHDRS motor score obtained closest to time of SDH was 51 (16 patients). Most SDH occurred in the context of ground level falls or using stairs although 5 patients had no history of head trauma. Additional brain injury may occur along with the SDH. The most common symptoms were altered mental status, hemiparesis and loss of consciousness. The over-representation of females in this study requires replication and further investigation. Conclusion: Patients with HD are at increased risk for SDH. An increased suspicion for SDH in HD patients should be considered, as this phenomenon may be initially unrecognized, may require extensive utilization of medical resources and is a potential cause of death. Show more

Keywords: Head trauma, subdural hematoma, Huntington’s disease, falls, chorea

DOI: 10.3233/JHD-210478

Citation: Journal of Huntington's Disease, vol. 10, no. 3, pp. 385-390, 2021

Authors: Fung, Susan | Smith, Carole L. | Prater, Katherine E. | Case, Amanda | Green, Kevin | Osnis, Leah | Winston, Chloe | Kinoshita, Yoshito | Sopher, Bryce | Morrison, Richard S. | Garden, Gwenn A. | Jayadev, Suman

Article Type: Research Article

Abstract: Background: Early-onset familial Alzheimer disease (EOFAD) is caused by heterozygous variants in the presenilin 1 (PSEN1 ), presenilin 2 (PSEN 2), and APP genes. Decades after their discovery, the mechanisms by which these genes cause Alzheimer’s disease (AD) or promote AD progression are not fully understood. While it is established that presenilin (PS) enzymatic activity produces amyloid-β (Aβ), PSs also regulate numerous other cellular functions, some of which intersect with known pathogenic drivers of neurodegeneration. Accumulating evidence suggests that microglia, resident innate immune cells in the central nervous system, play a key role in AD neurodegeneration. Objective: Previous work has …identified a regulatory role for PS2 in microglia. We hypothesized that PSEN2 variants lead to dysregulated microglia, which could further contribute to disease acceleration. To mimic the genotype of EOFAD patients, we created a transgenic mouse expressing PSEN2 N141I on a mouse background expressing one wildtype PS2 and two PS1 alleles. Results: Microglial expression of PSEN2 N141I resulted in impaired γ -secretase activity as well as exaggerated inflammatory cytokine release, NFκ B activity, and Aβ internalization. In vivo , PS2 N141I mice showed enhanced IL-6 and TREM2 expression in brain as well as reduced branch number and length, an indication of “activated” morphology, in the absence of inflammatory stimuli. LPS intraperitoneal injection resulted in higher inflammatory gene expression in PS2 N141I mouse brain relative to controls. Conclusion: Our findings demonstrate that PSEN2 N141I heterozygosity is associated with disrupted innate immune homeostasis, suggesting EOFAD variants may promote disease progression through non-neuronal cells beyond canonical dysregulated Aβ production. Show more

Keywords: Alzheimer’s disease, cytokine, glia, inflammation, microglia, phagocytosis, presenilin

DOI: 10.3233/JAD-200492

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 675-688, 2020

Authors: Latimer, Caitlin S. | Flanagan, Margaret E. | Cimino, Patrick J. | Jayadev, Suman | Davis, Marie | Hoffer, Zachary S. | Montine, Thomas J. | Gonzalez-Cuyar, Luis F. | Bird, Thomas D. | Keene, C. Dirk

Article Type: Research Article

Abstract: Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT ) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington’s disease (JHD), defined as HD arising before age 20, accounts for 5–10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington’s disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. Objective: The neuropathologic changes of AOHD are well characterized, but there are …fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy’s clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. Methods: A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Results: Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Conclusions: Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD. Show more

Keywords: Autopsy, huntingtin protein, Huntington’s disease, immunohistochemistry, juvenile Huntington’s disease, literature review, neuropathology

DOI: 10.3233/JHD-170261

Citation: Journal of Huntington's Disease, vol. 6, no. 4, pp. 337-348, 2017

Authors: Pearl, Jocelynn R. | Heath, Laura M. | Bergey, Dani E. | Kelly, John P. | Smith, Corrie | Laurino, Mercy Y. | Weiss, Avery | Price, Nathan D. | LaSpada, Albert | Bird, Thomas D. | Jayadev, Suman

Article Type: Research Article

Abstract: Background: Huntington’s disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD. Objective: The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease. Methods: Eighteen patients and 10 controls with inclusion criteria of ages 18–70 years (average age …HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject. Results: We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2 ). Conclusions: ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway. Show more

Keywords: Cone photoreceptor, electroretinogram, Huntington’s disease, retina

DOI: 10.3233/JHD-170255

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 237-247, 2017