α-Synuclein Heteromers in Red Blood Cells of Alzheimer’s Disease and Lewy Body Dementia Patients

2021 ◽  
Vol 80 (2) ◽  
pp. 885-893
Author(s):  
Simona Daniele ◽  
Filippo Baldacci ◽  
Rebecca Piccarducci ◽  
Giovanni Palermo ◽  
Linda Giampietri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Accuracy ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Lewy Body ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Lewy Body Dementia

Background: Red blood cells (RBCs) contain the majority of α-synuclein (α-syn) in blood, representing an interesting model for studying the peripheral pathological alterations proved in neurodegeneration. Objective: The current study aimed to investigate the diagnostic value of total α-syn, amyloid-β (Aβ1–42), tau, and their heteroaggregates in RBCs of Lewy body dementia (LBD) and Alzheimer’s disease (AD) patients compared to healthy controls (HC). Methods: By the use of enzyme-linked immunosorbent assays, RBCs concentrations of total α-syn, Aβ1–42, tau, and their heteroaggregates (α-syn/Aβ1–42 and α-syn/tau) were measured in 27 individuals with LBD (Parkinson’s disease dementia, n = 17; dementia with Lewy bodies, n = 10), 51 individuals with AD (AD dementia, n = 37; prodromal AD, n = 14), and HC (n = 60). Results: The total α-syn and tau concentrations as well as α-syn/tau heterodimers were significantly lower in the LBD group and the AD group compared with HC, whereas α-syn/Aβ1–42 concentrations were significantly lower in the AD dementia group only. RBC α-syn/tau heterodimers had a higher diagnostic accuracy for differentiating patients with LBD versus HC (AUROC = 0.80). Conclusion: RBC α-syn heteromers may be useful for differentiating between neurodegenerative dementias (LBD and AD) and HC. In particular, RBC α-syn/tau heterodimers have demonstrated good diagnostic accuracy for differentiating LBD from HC. However, they are not consistently different between LBD and AD. Our findings also suggest that α-syn, Aβ1–42, and tau interact in vivo to promote the aggregation and accumulation of each other.

scholarly journals α-Synuclein heteromers with ß-amyloid and tau decreased in red blood cells of Alzheimer’s disease and Lewy Body dementia patients.

2020 ◽  
Author(s):  
Simona Daniele ◽  
Filippo Baldacci ◽  
Rebecca Piccarducci ◽  
Giovanni Palermo ◽  
Linda Giampietri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Accuracy ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Lewy Body ◽  
In Vivo Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Elisa System

Abstract Background Red blood cells (RBC) account for more than 99% of α-syn concentrations in blood representing an interesting in vivo model for studying peripheral pathological alterations proved in neurodegeneration. The aim of the current study was to investigate the diagnostic value of total α-syn, Aβ 1-42 , tau and their heteroaggregates in RBCs of Lewy Body Dementias (LBDs) and Alzheimer’s disease (AD) patients compared to and healthy controls (HCs). Methods With a “home-made” sandwich enzyme-linked immunosorbent assay (ELISA) system, RBCs levels of total α-syn, Aβ 1-42 , tau and their heteroaggregates (α-syn/Aβ 1-42 and α-syn/tau) were measured in 27 subjects with LBDs (PDD, n = 17; DLB, n = 10), 51 subjects with AD (AD dementia, n = 37, prodromal AD, n = 14), and HC (n = 60). Results Compared with HC, total α-syn and tau concentrations as well as α-syn/tau heterodimers were significantly lower in LBDs group (p = 0.009, p = 0.009, and p < 0.001, respectively) and in AD group (p = 0.011, p = 0.003, and p < 0.001, respectively), whereas the heteroaggregates α-syn/Aβ 1-42 were significantly lower in AD dementia group (p < 0.001) only. RBC α-syn/tau heterodimers had the higher diagnostic accuracy for differentiating patients with LBD vs controls (AUROC = 0.80). Conclusion RBC α-syn heteroaggregates may be useful for differentiating between neurodegenerative dementias (LBD and AD) and healthy control. In particular, RBC α-syn/tau heterodimers have demonstrated good diagnostic accuracy for differentiating LBDs from HC. However, they are not consistently different between LBD and AD. Our findings also go beyond the clinical setting, suggesting that α-syn, Aβ 1-42 , and tau interact in vivo to promote the aggregation and accumulation of each other presumably accelerating cognitive dysfunction.

scholarly journals Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies

2009 ◽  
Vol 194 (1) ◽  
pp. 34-39 ◽  
Author(s):  
John T. O'Brien ◽  
Ian G. McKeith ◽  
Zuzana Walker ◽  
Klaus Tatsch ◽  
Jan Booij ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Accuracy ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Photon Emission ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Emission Computed Tomography

Background123I-FP-CIT SPECT (single photon emission computed tomography) can help in the differential diagnosis of probable dementia with Lewy bodies (Lewy body dementia) and Alzheimer's disease.AimsOur aim was to determine the accuracy of 123I-FP-CIT SPECT in diagnosing people with possible dementia with Lewy bodies.MethodWe undertook a 12-month follow-up of 325 individuals with probable or possible Lewy body or non-Lewy body dementia who had previously undergone 123I-FP-CIT SPECT. A consensus panel masked to SPECT findings, established diagnosis at 12 months in 264 people.ResultsOf 44 people with possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19 people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body dementia (16%) and for 18 individuals it remained possible dementia with Lewy bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7 individuals with a possible diagnosis who were diagnosed as having Alzheimer's disease at follow-up had normal scans (specificity 100%).ConclusionsOur findings confirm the diagnostic accuracy of 123I-FP-CIT SPECT in distinguishing Lewy body from non-Lewy body dementia and also suggest a clinically useful role in diagnostically uncertain cases, as an abnormal scan in a person with possible dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.

scholarly journals Collusion of α-Synuclein and Aβ aggravating co-morbidities in a novel prion-type mouse model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Grace M. Lloyd ◽  
Jess-Karan S. Dhillon ◽  
Kimberly-Marie M. Gorion ◽  
Cara Riffe ◽  
Susan E. Fromholt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Amyloid Β ◽  
Lewy Body Dementia ◽  
Immunohistochemical Analysis ◽  
Aggregation Kinetics ◽  
Current Area ◽  
Old Mice ◽  
A Current

Abstract Background The misfolding of host-encoded proteins into pathological prion conformations is a defining characteristic of many neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia. A current area of intense study is the way in which the pathological deposition of these proteins might influence each other, as various combinations of co-pathology between prion-capable proteins are associated with exacerbation of disease. A spectrum of pathological, genetic and biochemical evidence provides credence to the notion that amyloid β (Aβ) accumulation can induce and promote α-synuclein pathology, driving neurodegeneration. Methods To assess the interplay between α-synuclein and Aβ on protein aggregation kinetics, we crossed mice expressing human α-synuclein (M20) with APPswe/PS1dE9 transgenic mice (L85) to generate M20/L85 mice. We then injected α-synuclein preformed fibrils (PFFs) unilaterally into the hippocampus of 6-month-old mice, harvesting 2 or 4 months later. Results Immunohistochemical analysis of M20/L85 mice revealed that pre-existing Aβ plaques exacerbate the spread and deposition of induced α-synuclein pathology. This process was associated with increased neuroinflammation. Unexpectedly, the injection of α-synuclein PFFs in L85 mice enhanced the deposition of Aβ; whereas the level of Aβ deposition in M20/L85 bigenic mice, injected with α-synuclein PFFs, did not differ from that of mice injected with PBS. Conclusions These studies reveal novel and unexpected interplays between α-synuclein pathology, Aβ and neuroinflammation in mice that recapitulate the pathology of Alzheimer’s disease and Lewy body dementia.

Dementia with Lewy bodies

1998 ◽  
Vol 4 (6) ◽  
pp. 360-363 ◽  
Author(s):  
E. Jane Byrne
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Senile Dementia ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Body Type ◽  
Clinical Criteria ◽  
Dementia Syndrome ◽  
Distinct Disease

Dementia with cortical Lewy bodies (LBD) was first described by Okazakiet alin 1961 and is now recognised as a relatively common cause of the dementia syndrome. The true prevalence of LBD is unknown. In post-mortem studies of patients diagnosed as having dementia in life, the mean frequency of Lewy body dementia is 12.5% (Byrne, 1997). Clinically diagnosed LBD (using operational clinical criteria) is found in 10–23% of patients presenting to, or in the care of, psychogeriatric services (Collertonet al, 1996). What is not yet certain is its nosological status; opinion is divided between regarding it as a variety of Alzheimer's disease (the Lewy body variant), a distinct disease (senile dementia of the Lewy body type) or a spectrum disorder related to both Parkinson's disease and to Alzheimer's disease (Byrne, 1992).

scholarly journals Evidence of compensation in the brain networks of Lewy body dementia and Alzheimer’s disease patients

2017 ◽  
Author(s):  
Luis R. Peraza ◽  
Ruth Cromarty ◽  
Xenia Kobeleva ◽  
Michael J. Firbank ◽  
Alison Killen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Minimum Spanning Tree ◽  
Brain Networks ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Dominant Frequency ◽  
Compensatory Response ◽  
The Brain

AbstractDementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) require differential management despite presenting with symptomatic overlap. A human electrophysiological difference is a decrease of dominant frequency (DF) −the highest power frequency between 4-15Hz– in DLB; a characteristic of Parkinsonian diseases. We analysed electroencephalographic (EEG) recordings from old adults: healthy controls (HCs), AD, DLB and Parkinson’s disease dementia (PDD) patients. Brain networks were assessed with the minimum spanning tree (MST) within six EEG bands: delta, theta, high-theta, alpha, beta and DF. Patients showed lower alpha band connectivity and lower DF than HCs. Lewy body dementias showed a randomised MST compared with HCs and AD in high-theta and alpha but not within the DF. The MST randomisation in DLB and PDD reflects decreased brain efficiency as well as impaired neural synchronisation. However, the lack of network topology differences at the DF indicates a compensatory response of the brain to the neuropathology.

scholarly journals P.052 Understanding the influence of APOE-ɛ4 on magnetic resonance imaging-based hippocampal phenotypes in Alzheimer’s disease and Lewy body dementia

2021 ◽  
Vol 48 (s3) ◽  
pp. S34-S34
Author(s):  
U Saeed ◽  
P Desmarais ◽  
M Masellis
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Resonance ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Hippocampal Atrophy ◽  
Resonance Imaging

Background: The ɛ4-allele of apolipoprotein E (APOE-ɛ4) increases the risk not only for Alzheimer’s disease (AD), but also for Parkinson’s disease dementia and dementia with Lewy bodies (collectively, Lewy body dementia [LBD]). Hippocampal volume is an important neuroimaging biomarker for AD and LBD, although its association with APOE-ɛ4 is inconsistently reported. We investigated the association of APOE-ε4 with hippocampal atrophy quantified using magnetic resonance imaging in AD and LBD. Methods: Electronic databases (PubMed, Embase, PsycINFO, Scopus, Web of Science) were systematically searched for studies published up until December 31st, 2020. Results: Thirty-nine studies (25 cross-sectional, 14 longitudinal) were included. We observed that: (1) APOE-ε4 was associated with greater rate of hippocampal atrophy in AD and those who progressed from mild cognitive impairment to AD, (2) APOE-ε4 carriers showed greater involvement of cornu ammonis-1 hippocampal subfield versus non-carriers in AD, (3) APOE-ɛ4 may influence hippocampal atrophy in dementia with Lewy bodies, although longitudinal investigations are required, and (4) APOE-ε4 associated with earlier rather than very late expression of mediotemporal degeneration and memory-related neurocognitive impairment. Conclusions: The role of APOE-ɛ4 in modulating hippocampal phenotypes may be further clarified through more homogenous, well-powered, pathology-proven studies. Understanding the underlying mechanisms will facilitate development of prevention strategies targeting APOE-ɛ4.

scholarly journals Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies

2020 ◽  
pp. 1-7
Author(s):  
Gemma Roberts ◽  
Paul C. Donaghy ◽  
Jim Lloyd ◽  
Rory Durcan ◽  
George Petrides ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diagnostic Accuracy ◽  
Lewy Body ◽  
Photon Emission ◽  
Lewy Bodies ◽  
Positive Likelihood Ratio ◽  
Lewy Body Disease

Background Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. Aims To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. Method We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. Results At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3. Conclusions It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.

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