scholarly journals Association of Carotid and Intracranial Stenosis with Alzheimer’s Disease Biomarkers

2020 ◽  
Author(s):  
Koung Mi Kang ◽  
Min Soo Byun ◽  
Jun Ho Lee ◽  
Dahyun Yi ◽  
Hye Jeong Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Volume ◽  
Artery Stenosis ◽  
Intracranial Artery ◽  
Positron Emission ◽  
Intracranial Artery Stenosis ◽  
Intracranial Arteries ◽  
Demographic Covariates

Abstract Background To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer’s disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aβ) deposition and neurodegeneration in middle- and old-aged individuals. Given the differential progression of Aβ deposition and neurodegeneration across clinical stages of AD, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups.Methods A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [11C] Pittsburgh Compound B positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e. number and degree of narrowing) and location of stenosis.Results We found no associations between carotid and intracranial artery stenosis and cerebral Aβ burden in either CN or CI group. In terms of AD-related neurodegeneration, exploratory univariate analyses showed associations between the presence and severity of stenosis and neurodegeneration biomarkers of AD (i.e. reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both CN and CI groups. In confirmatory multivariate analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant.Conclusions Neither carotid nor intracranial artery stenosis appears to be associated with brain Aβ burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy. These observations support the importance of proper management of intracranial artery stenosis for delaying the progression of AD neurodegeneration and related cognitive decline.

scholarly journals Association of carotid and intracranial stenosis with Alzheimer’s disease biomarkers

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Koung Mi Kang ◽  
◽  
Min Soo Byun ◽  
Jun Ho Lee ◽  
Dahyun Yi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Volume ◽  
Artery Stenosis ◽  
Intracranial Artery ◽  
Positron Emission ◽  
Intracranial Artery Stenosis ◽  
Intracranial Arteries ◽  
Demographic Covariates

Abstract Background To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer’s disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aβ) deposition and neurodegeneration in middle- and old-aged individuals. Given different variations of the pathologies between cognitive groups, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups. Methods A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [11C] Pittsburgh compound B-positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e., number and degree of narrowing), and location of stenosis. Results We found no associations between carotid and intracranial artery stenosis and cerebral Aβ burden in either the CN or the CI group. In terms of neurodegeneration, exploratory univariable analyses showed associations between the presence and severity of stenosis and regional neurodegeneration biomarkers (i.e., reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both the CN and CI groups. In confirmatory multivariable analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant. Conclusions Neither carotid nor intracranial artery stenosis appears to be associated with brain Aβ burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy.

Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer’s Disease

2019 ◽  
Vol 19 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Timo Grimmer ◽  
Oliver Goldhardt ◽  
Igor Yakushev ◽  
Marion Ortner ◽  
Christian Sorg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Pittsburgh Compound B ◽  
Positron Emission ◽  
Amyloid Load ◽  
Alzheimer’S Pathology

Background: Neprilysin (NEP) cleaves amyloid-β 1–42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer’s disease patients. Results: CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer’s pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.

scholarly journals In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H positron emission tomography

2019 ◽  
Vol 47 (2) ◽  
pp. 390-402 ◽  
Author(s):  
Christine Bastin ◽  
Mohamed Ali Bahri ◽  
François Meyer ◽  
Marine Manard ◽  
Emma Delhaye ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
In Vivo Imaging ◽  
Emission Tomography ◽  
Synaptic Loss ◽  
Positron Emission

IC-P-024: A novel positron emission tomography contrast agent targeting cathepsin d shows preferential in vivo retention in an Alzheimer's disease mouse model

2015 ◽  
Vol 11 (7S_Part_1) ◽  
pp. P26-P27
Author(s):  
Jonatan A. Snir ◽  
Mojmir Suchy ◽  
Geron A. Bindseil ◽  
Blaine A. Chronik ◽  
Robert H.E. Hudson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Mouse Model ◽  
Contrast Agent ◽  
Cathepsin D ◽  
Emission Tomography ◽  
Positron Emission

O1-02-05: A novel positron emission tomography contrast agent targeting cathepsin d shows preferential in vivo retention in an Alzheimer's disease mouse model

2015 ◽  
Vol 11 (7S_Part_3) ◽  
pp. P128-P128
Author(s):  
Jonatan A. Snir ◽  
Mojmir Suchy ◽  
Geron A. Bindseil ◽  
Blaine A. Chronik ◽  
Robert H.E. Hudson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Mouse Model ◽  
Contrast Agent ◽  
Cathepsin D ◽  
Emission Tomography ◽  
Positron Emission

Emerging biology of the cholinergic system across the spectrum of Alzheimer's disease

2006 ◽  
Vol 18 (s1) ◽  
pp. S3-S16 ◽  
Author(s):  
Agneta Nordberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nicotinic Acetylcholine Receptors ◽  
Cholinergic System ◽  
Imaging Techniques ◽  
Positron Emission Tomography Imaging ◽  
Amyloid Plaques ◽  
Hippocampal Volume ◽  
Brain Morphology

The pathological processes that lead to Alzheimer's disease (AD) begin decades before the onset of dementia. Brain abnormalities in genetically susceptible individuals have been observed even in young adults. Patients with AD differ from normal elderly patients in brain morphology and neurochemistry. Important observations include increasing appearance of amyloid plaques and neurofibrillary tangles, progressive loss of hippocampal volume, reduced cerebral glucose utilization, inflammatory processes, glial activation, and impairment of cholinergic function with losses of nicotinic acetylcholine receptors. These changes appear to begin in the asymptomatic stages and continue as cognition and then function and behavior are disrupted. Mild cognitive impairment (MCI) may be the first cognitive manifestation of this pathogenic process moderated by ongoing compensatory neurochemical mechanisms in the cholinergic system. Recent advances in positron emission tomography imaging techniques, including the development of the Pittsburgh B compound (PIB), allow in vivo visualization of amyloid plaques. These techniques have the potential to enable brain amyloid load to be monitored over time and to be related to brain function. Emerging evidence suggests that β-amyloid may interact with nicotinic receptors. This interaction may have clinically significant downstream effects and may mediate amyloid neurotoxicity. The cholinesterase inhibitors may have multiple actions, depending on the stage of the disease, from very mild to severe.

scholarly journals Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

2020 ◽  
Vol 12 (524) ◽  
pp. eaau5732 ◽  
Author(s):  
Renaud La Joie ◽  
Adrienne V. Visani ◽  
Suzanne L. Baker ◽  
Jesse A. Brown ◽  
Viktoriya Bourakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Specific Distribution ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
Β Amyloid ◽  
Tau Pet ◽  
Prospective Longitudinal

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

scholarly journals Combined Study of Cerebral Glucose Metabolism and [11C]Methionine Accumulation in Probable Alzheimer's Disease Using Positron Emission Tomography

1996 ◽  
Vol 16 (3) ◽  
pp. 399-408 ◽  
Author(s):  
E. Salmon ◽  
M. C. Gregoire ◽  
G. Delfiore ◽  
C. Lemaire ◽  
C. Degueldre ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Glucose Metabolism ◽  
Clinical Symptoms ◽  
Synaptic Activity ◽  
Emission Tomography ◽  
Tissue Loss ◽  
Positron Emission

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measured with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.

scholarly journals Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline

Neurology ◽  
2017 ◽  
Vol 89 (21) ◽  
pp. 2176-2186 ◽  
Author(s):  
Shannon L. Risacher ◽  
Wesley H. Anderson ◽  
Arnaud Charil ◽  
Peter F. Castelluccio ◽  
Sergey Shcherbinin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Alzheimer Disease ◽  
Volume Ratio ◽  
Hippocampal Volume ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Categorical Models

Objective:To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline.Methods:Amyloid-positive participants with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD [tADMRI]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models.Results:When participants were divided categorically, the HpSpMRI group showed significantly more AD-like hypometabolism on 18F-fluorodeoxyglucose-PET (p < 0.05) and poorer baseline executive function (p < 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSpMRI also showed faster subsequent clinical decline than participants with LPMRI on the Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog13), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tADMRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog13 score (p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy.Conclusions:AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.

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