scholarly journals Cortical Metabolism, Acetylcholinesterase Staining and Pathological Changes in Alzheimers Disease

1986 ◽  
Vol 13 (S4) ◽  
pp. 511-516 ◽  
Author(s):  
E.G. McGeer ◽  
P.L. McGeer ◽  
H. Kamo ◽  
H. Tago ◽  
R. Harrop
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Metabolic Rate ◽  
Senile Plaques ◽  
Variable Regions ◽  
Positron Emission ◽  
Highly Sensitive ◽  
Acetylcholinesterase Staining ◽  
Cortical Regions

Abstract:The local cerebral metabolic rate for glucose (LCMRgl) was determined by positron emission tomography (PET) using the 18F-fluorodeoxyglucose method in a series of Alzheimer patients and normal controls. The LCMRgl declined in the cerebral cortex with age, but the decrement was significantly greater in the clinically diagnosed Alzheimer's cases. Comparison of PET and psychological data indicated that, as the disease progressed clinically, the reduction in cortical LCMRgl and the number of cortical regions involved also increased. Variable regions of cortex were involved in the early stages but the temporal, parietal and frontal regions were most typically affected. One case coming to autopsy showed that the severity of the LCMRgl decline paralleled loss of neurons in the cortex and their replacement with astroglia.A case of Pick's disease coming to autopsy had shown a different and highly characteristic pattern of cortical metabolic defect. In this case also a poor metabolic rate was associated with extensive gliosis.Acetylcholinesterase (AChE) staining of the cerebral cortex in elderly normals and Alzheimer's disease cases with a new, highly sensitive method showed that in Alzheimer's disease there was an extensive loss of AChE-positive fibers with senile plaques frequently incorporating AChE-positive fiber debris. AChE staining of the substantia innominata area, where the cells giving rise to these neocortical fibers are presumably located, also showed evidence of degenerating cells and fibers.

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 Asymmetric Amyloid-β Burden and Neurodegeneration in Late-Onset Alzheimer’s Disease Dementia

2021 ◽  
Vol 39 (3) ◽  
pp. 197-201
Author(s):  
Joonho Lee ◽  
Hong Nam Kim ◽  
Min Hye Kim ◽  
In Ja Shin ◽  
Keun Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Brain Magnetic Resonance Imaging ◽  
Amyloid Β ◽  
Amyloid Deposition ◽  
Positron Emission ◽  
Amyloid Load ◽  
Cortical Regions ◽  
The Right

We report herein a 78-year-old woman with insidiously progressive cognitive impairment and asymmetric amyloid deposition and neurodegeneration. Brain magnetic resonance imaging revealed remarkable atrophy in the right-sided temporal lobe and hippocampus. Early dynamic <sup>18</sup>F-flutemetamol brain amyloid positron-emission tomography images showed decreased uptake in the right temporoparietal regions. Delayed images revealed amyloid deposition which was most remarkable in the right frontotemporoparietal regions. Asymmetries of amyloid burden and neuronal dysfunction are positively correlated in Alzheimer’s disease in cortical regions with high amyloid load.

scholarly journals Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
James M. Roe ◽  
◽  
Didac Vidal-Piñeiro ◽  
Øystein Sørensen ◽  
Andreas M. Brandmaier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Temporal Dynamics ◽  
Higher Order ◽  
Adult Lifespan ◽  
Organizational Principle ◽  
Cortical Regions ◽  
High Consistency ◽  
Cortical Asymmetry

AbstractAging and Alzheimer’s disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Asymmetry-change was further accelerated in AD. Results suggest a system-wide dedifferentiation of the adaptive asymmetric organization of heteromodal cortex in aging and AD.

scholarly journals Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load

2021 ◽  
Author(s):  
Valeria Calsolaro ◽  
Paul M. Matthews ◽  
Cornelius K. Donat ◽  
Nicholas R. Livingston ◽  
Grazia D. Femminella ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Late Onset ◽  
Visual Assessment ◽  
Glial Fibrillary Acid Protein ◽  
Pet Tracer ◽  
Positron Emission ◽  
Cortical Regions

Abstract11C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer’s disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), 18F-florbetaben and 11C-BU99008 PET. The 8 amyloid (Aβ)-positive CI subjects had higher 11C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11C-BU99008 and 18F-florbetaben. Autoradiography using 3H-BU99008 with post-mortem Alzheimer’s brains confirmed through visual assessment that increased 3H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that 11C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer’s disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aβ load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.

scholarly journals 18F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

2020 ◽  
Author(s):  
Mark D. Meadowcroft ◽  
Carson J. Purnell ◽  
Jian-Li Wang ◽  
Prasanna Karunanayaka ◽  
Qing X. Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Olfactory System ◽  
Clinical Symptoms ◽  
Piriform Cortex ◽  
Nucleus Accumbens Shell ◽  
Positron Emission ◽  
Neuronal Connections ◽  
Cortical Regions ◽  
Functional Investigation

AbstractCerebellar involvement in Alzheimer’s disease (AD) has not been studied to the extent that cortical neuropathological changes have. Historical and recent histopathological literature demonstrate cerebellar AD pathology while functional investigation has demonstrated disrupted intrinsic cortical – cerebellar connectivity in AD. Additionally, olfactory deficits occur early in AD, prior to the onset of clinical symptoms. The neurological basis for the involvement of the cerebellum and olfactory system in the disease course remain unclear. 18F-fludeoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed to characterize metabolism in the cerebellum and olfactory region of AD, mild-cognitive impaired (MCI), and age-matched cognitively normal (CN) controls. In contrast to known parietal and temporal lobe FDG hypo-metabolism within the default mode network in AD, a significant FDG hyper-metabolism was found in the cerebellum and olfactory cortical regions (including the piriform cortex, olfactory tubercle, anterior olfactory nucleus, and nucleus accumbens shell). The increase in cerebellum glucose utilization was shown also in late- verses early-MCI patients. The cerebellar and olfactory regions both contain inhibitory distal and inter-neuronal connections that are vulnerable to disruption in AD. The hyper-metabolism in the cerebellum and olfactory structures may reflect disruption of local and system-wide inhibitory networks due to AD neurodegeneration, suggesting a hypothetical mechanism for susceptibility of the olfactory system to early AD pathology.

scholarly journals Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer’s Disease

2016 ◽  
Vol 22 (10) ◽  
pp. 978-990 ◽  
Author(s):  
Emily C. Edmonds ◽  
Katherine J. Bangen ◽  
Lisa Delano-Wood ◽  
Daniel A. Nation ◽  
Ansgar J. Furst ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Standardized Uptake Value ◽  
Imaging Biomarkers ◽  
Preclinical Alzheimer’S Disease ◽  
Preclinical Ad ◽  
Novel Approach ◽  
Positron Emission ◽  
Subcortical Regions ◽  
Cortical Regions

AbstractObjectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods: A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978–990)

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Biological Signatures of Alzheimer’s Disease

2020 ◽  
Vol 20 (9) ◽  
pp. 770-781 ◽  
Author(s):  
Poornima Sharma ◽  
Anjali Sharma ◽  
Faizana Fayaz ◽  
Sharad Wakode ◽  
Faheem H. Pottoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Senile Plaque ◽  
Senile Plaques ◽  
Amyloid Deposition ◽  
Immune Defense ◽  
Amyloid Angiopathy ◽  
Microvascular Changes ◽  
Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

Sign in / Sign up

Export Citation Format

Share Document