scholarly journals The PET tracer [ 11 C]MK-6884 quantifies M4 muscarinic receptor in rhesus monkeys and patients with Alzheimer’s disease

2022 ◽  
Vol 14 (627) ◽  
Author(s):  
Wenping Li ◽  
Yuchuan Wang ◽  
Talakad G. Lohith ◽  
Zhizhen Zeng ◽  
Ling Tong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Muscarinic Receptor ◽  
Rhesus Monkeys ◽  
Target Engagement ◽  
Pet Tracer ◽  
M4 Muscarinic Receptor

[ 11 C]MK-6884 is an M4R-specific PET tracer for quantifying target engagement in brain and providing insights into AD neuropathology.

P2-027: TARGET ENGAGEMENT IN A PHASE II CLINICAL TRIAL OF AAV2-NGF GENE THERAPY FOR ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_12) ◽  
pp. P677-P677
Author(s):  
Michael J. Castle ◽  
Fernando Calvo Baltanas ◽  
Imre Kovacs ◽  
Alan H. Nagahara ◽  
Krystof S. Bankiewicz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Clinical Trial ◽  
Target Engagement ◽  
Ngf Gene

scholarly journals Evaluation of the novel 18 F‐labeled PET tracer SMBT‐1 for imaging astrogliosis in healthy elderly controls and A+/T+/(N+) Alzheimer's disease patients

2020 ◽  
Vol 16 (S4) ◽  
Author(s):  
Victor LL Villemagne ◽  
Ryuichi Harada ◽  
Vincent Dore ◽  
Shozo Furumoto ◽  
Rachel S Mulligan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Novel ◽  
Healthy Elderly ◽  
Pet Tracer

Estrogenic Regulation of Synaptic Health and Cognition in Aging Rhesus Monkeys

2020 ◽  
pp. 303-334
Author(s):  
Johanna L. Crimins ◽  
Yuko Hara ◽  
John H. Morrison
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Aging ◽  
Rhesus Monkeys ◽  
Memory Systems ◽  
Brain Regions ◽  
Clinical Literature ◽  
Menopausal Women ◽  
Dorsolateral Prefrontal ◽  
Estrogenic Regulation

A compelling case can be made for estrogen’s role in maintaining synaptic health in the context of cognitive aging. This chapter first reviews clinical literature pertinent to estrogenic actions on cognition in menopausal women. Next, the authors provide a comprehensive summary of recent investigations in aging rhesus monkeys, which have emerged as a particularly powerful model for the study of synaptic and cognitive effects of both natural and surgical menopause. In particular, we focus on hippocampal and dorsolateral prefrontal cortex neurons and circuits that degenerate in normal aging and Alzheimer’s disease. The responsiveness of these brain regions to estrogen and implications for their related memory systems are discussed. Finally, the chapter highlights work that needs to be done to more fully understand the molecular basis for the complex interplay between menopause, aging, and vulnerability to Alzheimer’s disease in higher cognitive function and synaptic health.

scholarly journals Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer’s disease

2020 ◽  
Vol 47 (13) ◽  
pp. 3176-3185
Author(s):  
Mark E. Schmidt ◽  
Luc Janssens ◽  
Diederik Moechars ◽  
Frederik J. R. Rombouts ◽  
Maarten Timmers ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Subjects ◽  
Graphical Analysis ◽  
Whole Body ◽  
Healthy Controls ◽  
Pet Tracer ◽  
Cortical Regions ◽  
Pet Scans ◽  
Pet Amyloid

Abstract Purpose The accumulation of misfolded tau is a common feature of several neurodegenerative disorders, with Alzheimer’s disease (AD) being the most common. Earlier we identified JNJ-64326067, a novel isoquinoline derivative with high affinity and selectivity for tau aggregates from human AD brain. We report the dosimetry of [18F] JNJ-64326067 and results of a proof-of-concept study comparing subjects with probable Alzheimer’s disease to age-matched healthy controls. Methods [18F] JNJ-64326067 PET scans were acquired for 90 min and then from 120 to 180 min in 5 participants with [18F]-florbetapir PET amyloid positive probable AD (73 ± 9 years) and 5 [18F]-florbetapir PET amyloid negative healthy controls (71 ± 7 years). Whole-body [18F] JNJ-64326067 PET CT scans were acquired in six healthy subjects for 5.5 h in 3 scanning sessions. Brain PET scans were visually reviewed. Regional quantification included kinetic analysis of distribution volume ration (DVR) estimated by Logan graphical analysis over the entire scan and static analysis of SUVr in late frames. Both methods used ventral cerebellar cortex as a reference region. Results One of the healthy controls had focal areas of PET signal in occipital and parietal cortex underlying the site of a gunshot injury as an adolescent; the other four healthy subjects had no tau brain signal. Four of the 5 AD participants had visually apparent retention of [18F] JNJ-64326067 in relevant cortical regions. One of the AD subjects was visually negative. Cortical signal in visually positive subjects approached steady state by 120 min. Temporal and frontal cortical SUVr/DVR values in visually positive AD subjects ranged from 1.21 to 3.09/1.2 to 2.18 and from 0.92 to 1.28/0.91 to 1.16 in healthy controls. Whole-body effective dose was estimated to be 0.0257 mSv/MBq for females and 0.0254 mSv/MBq for males. Conclusions [18F] JNJ-64326067 could be useful for detection and quantitation of tau aggregates.

scholarly journals Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation

2020 ◽  
Vol 21 (12) ◽  
pp. 4443
Author(s):  
Hiroyuki Shimada ◽  
Shinobu Minatani ◽  
Jun Takeuchi ◽  
Akitoshi Takeda ◽  
Joji Kawabe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Neuronal Degeneration ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Familial Alzheimer’S Disease ◽  
Pet Tracer ◽  
Familial Alzheimer's Disease ◽  
Parietal Cortices

We previously identified a novel mutation in amyloid precursor protein from a Japanese pedigree of familial Alzheimer’s disease, FAD (Osaka). Our previous positron emission tomography (PET) study revealed that amyloid β (Aβ) accumulation was negligible in two sister cases of this pedigree, indicating a possibility that this mutation induces dementia without forming senile plaques. To further explore the relationship between Aβ, tau and neurodegeneration, we performed tau and Aβ PET imaging in the proband of FAD (Osaka) and in patients with sporadic Alzheimer’s disease (SAD) and healthy controls (HCs). The FAD (Osaka) patient showed higher uptake of tau PET tracer in the frontal, lateral temporal, and parietal cortices, posterior cingulate gyrus and precuneus than the HCs (>2.5 SD) and in the lateral temporal and parietal cortices than the SAD patients (>2 SD). Most noticeably, heavy tau tracer accumulation in the cerebellum was found only in the FAD (Osaka) patient. Scatter plot analysis of the two tracers revealed that FAD (Osaka) exhibits a distinguishing pattern with a heavy tau burden and subtle Aβ accumulation in the cerebral cortex and cerebellum. These observations support our hypothesis that Aβ can induce tau accumulation and neuronal degeneration without forming senile plaques.

scholarly journals The acute effects of dimebolin, a potential Alzheimer's disease treatment, on working memory in rhesus monkeys

2011 ◽  
Vol 164 (3) ◽  
pp. 970-978 ◽  
Author(s):  
Scott J Webster ◽  
Christina A Wilson ◽  
Chih-Hung Lee ◽  
Eric G Mohler ◽  
Alvin V Terry Jr ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Rhesus Monkeys ◽  
Acute Effects ◽  
Disease Treatment

[P1-109]: MATHEMATICAL MODEL OF AMYLOID BETA (Aβ) DYNAMICS TO ASSESS TARGET ENGAGEMENT OF SOLUBLE Aβ OLIGOMERS BY CRENEZUMAB IN THE ALZHEIMER's DISEASE BRAIN

2017 ◽  
Vol 13 (7S_Part_5) ◽  
pp. P282-P282
Author(s):  
Gregory Z. Ferl ◽  
Reina N. Fuji ◽  
Jasvinder Atwal ◽  
Saroja Ramanujan ◽  
Angelica Quartino
Keyword(s):  
Alzheimer’S Disease ◽  
Mathematical Model ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Target Engagement ◽  
Aβ Oligomers ◽  
Soluble Aβ Oligomers

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

scholarly journals The Retinal Inner Plexiform Synaptic Layer Mirrors Grey Matter Thickness of Primary Visual Cortex with Increased Amyloid β Load in Early Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Lília Jorge ◽  
Nádia Canário ◽  
Ricardo Martins ◽  
Beatriz Santiago ◽  
Isabel Santana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Early Stage ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Binding Potential ◽  
Inner Plexiform Layer ◽  
Pet Tracer

The retina may serve as putative window into neuropathology of synaptic loss in Alzheimer’s disease (AD). Here, we investigated synapse-rich layers versus layers composed by nuclei/cell bodies in an early stage of AD. In addition, we examined the associations between retinal changes and molecular and structural markers of cortical damage. We recruited 20 AD patients and 17 healthy controls (HC). Combining optical coherence tomography (OCT), magnetic resonance (MR), and positron emission tomography (PET) imaging, we measured retinal and primary visual cortex (V1) thicknesses, along with V1 amyloid β (Aβ) retention ([11C]-PiB PET tracer) and neuroinflammation ([11C]-PK11195 PET tracer). We found that V1 showed increased amyloid-binding potential, in the absence of neuroinflammation. Although thickness changes were still absent, we identified a positive association between the synapse-rich inner plexiform layer (IPL) and V1 in AD. This retinocortical interplay might reflect changes in synaptic function resulting from Aβ deposition, contributing to early visual loss.

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