Association of butyrylcholinesterase K variant with cholinesterase-positive neuritic plaques in the temporal cortex in late-onset Alzheimer's disease

2000 ◽  
Vol 106 (4) ◽  
pp. 447-452 ◽  
Author(s):  
Donald J. Lehmann ◽  
Zsuzsanna Nagy ◽  
Suzanne Litchfield ◽  
Mario Cortina Borja ◽  
A. David Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Temporal Cortex ◽  
Neuritic Plaques ◽  
K Variant

scholarly journals Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

2016 ◽  
Vol 113 (42) ◽  
pp. E6535-E6544 ◽  
Author(s):  
Xiuming Zhang ◽  
Elizabeth C. Mormino ◽  
Nanbo Sun ◽  
Reisa A. Sperling ◽  
Mert R. Sabuncu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Bayesian Model ◽  
Late Onset ◽  
Temporal Cortex ◽  
Cortical Atrophy ◽  
Future Research ◽  
Dementia Patients ◽  
With Memory

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

Relation between neuritic plaques and depressive state in Alzheimer's disease

2010 ◽  
Vol 22 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Gerben Meynen ◽  
Heleen Van Stralen ◽  
Jan H. Smit ◽  
Wouter Kamphorst ◽  
Dick F. Swaab ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Temporal Cortex ◽  
Clinical Severity ◽  
Depressive State ◽  
Neuritic Plaques ◽  
Prospective Longitudinal Study ◽  
Severity Of Dementia ◽  
Prospective Longitudinal

Meynen G, Van Stralen H, Smit JH, Kamphorst W, Swaab DF, Hoogendijk WJG. Relation between neuritic plaques and depressive state in Alzheimer's disease.Background:To investigate for the first time in a prospective study the relationship between depressive state and the neuropathological hallmarks of Alzheimer's disease, using a scale for depressive symptoms in dementia, while controlling for clinical severity of dementia.Method:Within the framework of a prospective longitudinal study of depression in Alzheimer's disease, patients with dementia underwent a clinical evaluation every six months during the last years of their lives, using the Cornell scale for depression in dementia to assess depressive symptoms and using the Functional Assessment Staging scale to control for clinical severity of dementia. The brains of 43 Alzheimer patients were obtained. The last clinical evaluations prior to death together with post-mortem neuropathology measures were analysed.Results:We found a correlation between the Cornell scores and the sum score for the density of neuritic plaques in the entire cortex (p = 0.027), and even stronger in the temporal cortex (p = 0.012). The observed correlations were independent of sex, age of death, clinical dementia severity and duration of Alzheimer's disease.Conclusions:This study shows a positive relationship between depressive state at time of death and the presence of neuritic plaques in Alzheimer's disease, which is independent of the clinical severity of dementia.

scholarly journals Postmortem Neocortical 3H-PiB Binding and Levels of Unmodified and Pyroglutamate Aβ in Down Syndrome and Sporadic Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Violetta N. Pivtoraiko ◽  
Tamara Racic ◽  
Eric E. Abrahamson ◽  
Victor L. Villemagne ◽  
Benjamin L. Handen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Late Onset ◽  
Amyloid Β ◽  
Molecular Profile ◽  
Amyloid Angiopathy ◽  
Neuritic Plaques ◽  
Amyloid Deposits

Individuals with Down syndrome (DS) have a genetic predisposition for amyloid-β (Aβ) overproduction and earlier onset of Aβ deposits compared to patients with sporadic late-onset Alzheimer’s disease (AD). Positron emission tomography (PET) with Pittsburgh Compound-B (PiB) detects fibrillar Aβ pathology in living people with DS and AD, but its relationship with heterogeneous Aβ forms aggregated within amyloid deposits is not well understood. We performed quantitative in vitro3H-PiB binding assays and enzyme-linked immunosorbent assays of fibrillar (insoluble) unmodified Aβ40 and Aβ42 forms and N-terminus truncated and pyroglutamate-modified AβNpE3-40 and AβNpE3-42 forms in postmortem frontal cortex and precuneus samples from 18 DS cases aged 43–63 years and 17 late-onset AD cases aged 62–99 years. Both diagnostic groups had frequent neocortical neuritic plaques, while the DS group had more severe vascular amyloid pathology (cerebral amyloid angiopathy, CAA). Compared to the AD group, the DS group had higher levels of Aβ40 and AβNpE3-40, while the two groups did not differ by Aβ42 and AβNpE3-42 levels. This resulted in lower ratios of Aβ42/Aβ40 and AβNpE3-42/AβNpE3-40 in the DS group compared to the AD group. Correlations of Aβ42/Aβ40 and AβNpE3-42/AβNpE3-40 ratios with CAA severity were strong in DS cases and weak in AD cases. Pyroglutamate-modified Aβ levels were lower than unmodified Aβ levels in both diagnostic groups, but within group proportions of both pyroglutamate-modified Aβ forms relative to both unmodified Aβ forms were lower in the DS group but not in the AD group. The two diagnostic groups did not differ by 3H-PiB binding levels. These results demonstrate that compared to late-onset AD cases, adult DS individuals with similar severity of neocortical neuritic plaques and greater CAA pathology have a preponderance of both pyroglutamate-modified AβNpE3-40 and unmodified Aβ40 forms. Despite the distinct molecular profile of Aβ forms and greater vascular amyloidosis in DS cases, cortical 3H-PiB binding does not distinguish between diagnostic groups that are at an advanced level of amyloid plaque pathology. This underscores the need for the development of CAA-selective PET radiopharmaceuticals to detect and track the progression of cerebral vascular amyloid deposits in relation to Aβ plaques in individuals with DS.

scholarly journals Butyrylcholinesterase Protein Ends in the Pathogenesis of Alzheimer’s Disease—Could BCHE Genotyping Be Helpful in Alzheimer’s Therapy?

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 592 ◽  
Author(s):  
Jacek Jasiecki ◽  
Bartosz Wasąg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Enzyme Activity ◽  
Late Onset ◽  
Past Century ◽  
Nucleotide Polymorphisms ◽  
Amino Acid Residues ◽  
Patients At Risk ◽  
K Variant

Late-onset Alzheimer’s disease (AD) is clinically characterized by a progressive decline of memory and other cognitive functions leading to the loss of the ability to perform everyday activities. Only a few drugs have been approved to treat AD dementia over the past century since the first AD patient was diagnosed. Drugs increasing the availability of neurotransmitters at synapses in the brain are used clinically in the treatment of AD dementia, and cholinesterase inhibitors (ChEIs) are the mainstay of the therapy. A detrimental effect on cognitive function has been reported in patients with pharmacological inhibition of acetylcholinesterase (AChE) by ChEIs and reduced butyrylcholinesterase (BChE) activity due to the single nucleotide polymorphisms. The BChE K-variant (rs1803274), the most common genetic variant of the BCHE gene, was thought to reduce enzyme activity reflecting the lower clinical response to rivastigmine in AD patients. During ChEIs therapy, patients carrying reduced-activity BChE do not present such improved attention like patients with the wild-type enzyme. On the other hand, alterations in the BCHE gene causing enzyme activity reduction may delay AD onset in patients at risk by preserving the level of cortical acetylcholine (ACh). Based on our previous results, we conclude that SNPs localized outside of the coding sequence, in 5’UTR (rs1126680) and/or intron 2 (rs55781031) of the BCHE gene, but not solely K-variant alteration (p.A539T) itself, are responsible for reduced enzyme activity. Therefore, we suspect that not BChE-K itself, but these coexisting SNPs (rs1126680 and rs55781031), could be associated with deleterious changes in cognitive decline in patients treated with ChEIs. Based on the results, we suggest that SNPs (rs1126680) and/or (rs55781031) genotyping should be performed to identify subjects at risk for lowered efficacy ChEIs therapy, and such patients should be treated with a lower rivastigmine dosage. Finally, our sequence analysis of the N-terminal end of N-BChE revealed evolutionarily conserved amino acid residues that can be involved in disulfide bond formation and anchoring of N-BChE in the cell membrane.

K variant of butyrycholinesterase and late-onset Alzheimer's disease

The Lancet ◽  
1998 ◽  
Vol 351 (9106) ◽  
pp. 881 ◽  
Author(s):  
C Russ ◽  
J Powell ◽  
S Lovestone ◽  
C Holmes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
K Variant

scholarly journals Synergy between the alteration in the N-terminal region of butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jacek Jasiecki ◽  
Anna Limon-Sztencel ◽  
Monika Żuk ◽  
Magdalena Chmara ◽  
Dominik Cysewski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Terminal Region ◽  
Apolipoprotein E4 ◽  
K Variant

scholarly journals Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

2016 ◽  
Author(s):  
Xiuming Zhang ◽  
Elizabeth C. Mormino ◽  
Nanbo Sun ◽  
Reisa A. Sperling ◽  
Mert R. Sabuncu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Bayesian Model ◽  
Late Onset ◽  
Temporal Cortex ◽  
Cortical Atrophy ◽  
Individual Level ◽  
Dementia Patients ◽  
With Memory

AbstractWe employed a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural magnetic resonance imaging (MRI) of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus and amygdala), a subcortical atrophy factor (striatum, thalamus and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, while the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared to temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Code from this manuscript is publicly available at link_to_be_added.

Sign in / Sign up

Export Citation Format

Share Document