scholarly journals Brain Shape Changes Associated With Cerebral Atrophy in Healthy Aging and Alzheimer’s Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Yana Blinkouskaya ◽  
Johannes Weickenmeier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Morphological Changes ◽  
Deformation Gradient ◽  
Cerebral Atrophy ◽  
Cellular Aging ◽  
Atrophy Rate ◽  
Brain Shape

Both healthy and pathological brain aging are characterized by various degrees of cognitive decline that strongly correlate with morphological changes referred to as cerebral atrophy. These hallmark morphological changes include cortical thinning, white and gray matter volume loss, ventricular enlargement, and loss of gyrification all caused by a myriad of subcellular and cellular aging processes. While the biology of brain aging has been investigated extensively, the mechanics of brain aging remains vastly understudied. Here, we propose a multiphysics model that couples tissue atrophy and Alzheimer’s disease biomarker progression. We adopt the multiplicative split of the deformation gradient into a shrinking and an elastic part. We model atrophy as region-specific isotropic shrinking and differentiate between a constant, tissue-dependent atrophy rate in healthy aging, and an atrophy rate in Alzheimer’s disease that is proportional to the local biomarker concentration. Our finite element modeling approach delivers a computational framework to systematically study the spatiotemporal progression of cerebral atrophy and its regional effect on brain shape. We verify our results via comparison with cross-sectional medical imaging studies that reveal persistent age-related atrophy patterns. Our long-term goal is to develop a diagnostic tool able to differentiate between healthy and accelerated aging, typically observed in Alzheimer’s disease and related dementias, in order to allow for earlier and more effective interventions.

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

scholarly journals Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Shouneng Peng ◽  
Lu Zeng ◽  
Jean-Vianney Haure-Mirande ◽  
Minghui Wang ◽  
Derek M. Huffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Normal Aging ◽  
Aging Brain ◽  
Normal Brain ◽  
Older Individuals ◽  
Cognitively Normal

Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between aging and LOAD. We found that shared gene expression changes between aging and LOAD are mostly seen in the hippocampal and several cortical regions. In the hippocampus, the expression of phosphoprotein, alternative splicing and cytoskeleton genes are commonly changed in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are more related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also found that normal aging brain transcriptomes from relatively young donors (45–70 years old) clustered into several subgroups and some subgroups showed gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptomic datasets from another cohort of older individuals (>70 years), we found that samples from cognitively normal older individuals clustered with the “healthy aging” subgroup while AD samples mainly clustered with the “AD similar” subgroups. This may imply that individuals in the healthy aging subgroup will likely remain cognitively normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitively normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the “normal brain aging” to identify the very early molecular events that may lead to LOAD development.

scholarly journals Transcriptomic changes highly similar to Alzheimer's disease are observed in a subpopulation of individuals during normal brain aging

2021 ◽  
Author(s):  
Shouneng Peng ◽  
Lu Zeng ◽  
Jean-vianney Haure-mirande ◽  
Minghui Wang ◽  
Derek M. Huffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Healthy Aging ◽  
Brain Aging ◽  
Late Onset ◽  
Normal Aging ◽  
Normal Brain ◽  
Older Individuals

Aging is a major risk factor for late-onset Alzheimer's disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examine multiple large-scale human brain transcriptomic data from both normal aging and LOAD to understand the molecular interconnection between aging and LOAD. We find that shared gene expression changes between aging and LOAD are mostly seen in the hippocampus and several cortical regions. In the hippocampus, phosphoprotein, alternative splicing and cytoskeleton are the commonly dysregulated biological pathways in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also find that normal aging brains from relatively young donors (45-70 years old) cluster into subgroups and some subgroups show gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptome data from older individuals (>70 years), we find that samples from cognitive normal older individuals cluster with the "healthy aging" subgroup while AD samples mainly cluster with the AD similar subgroups. This implies that individuals in the healthy aging subgroup will likely remain cognitive normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitive normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the "normal brain aging" in a subgroup of individuals in their 40s-60s to identify the very early events in LOAD development.

scholarly journals Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer’s Disease Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Rui Zheng ◽  
Yang-mei Huang ◽  
Qiang Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Inflammatory Responses ◽  
Brain Aging ◽  
Lymphatic Vessels ◽  
Amyloid Β ◽  
Brain Functions ◽  
Vital Functions ◽  
The Brain

Recent studies have revealed significant contributions of lymphatic vessels (LVs) to vital functions of the brain, especially related to clearance of waste from the brain and immune responses in the brain. These studies collectively indicate that enhancing the functions of LVs may improve brain functions during brain aging and in Alzheimer’s disease (AD) where LV functions are impaired. However, it is currently unknown whether this enhancement can be achieved using small molecules. We have previously shown that a widely used Chinese herbal medicine Xueshuantong (XST) significantly improves functions and reduces pathology in AD transgenic mice associated with elevated cerebral blood flow (CBF). Here, we show that XST partially rescues deficits in lymphatic structures, improves clearance of amyloid-β (Aβ) from the brain, and reduces the inflammatory responses in the serum and brains of transgenic AD mice. In addition, we showed that this improvement in the lymphatic system occurs independently of elevated CBF, suggesting independent modulation and limited interaction between blood circulation and lymphatic systems. Moreover, XST treatment leads to a significant increase in GLT-1 level and a significantly lower level of MMP-9 and restores AQP4 polarity in APP/PS1 mice. These results provide the basis for further exploration of XST to enhance or restore LV functions, which may be beneficial to treat neurodegenerative diseases or promote healthy aging.

Voxel-based morphometry (VBM) analysis in Alzheimer's disease an insight into heterogeneity of cerebral atrophy

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S338-S338
Author(s):  
Akihiko Shiino ◽  
Toshiyuki Watanabe ◽  
Ichiro Akiguchi ◽  
Shigehiro Morikawa ◽  
Toshiro Inubushi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Atrophy ◽  
Voxel Based Morphometry ◽  
Insight Into

Alzheimer’s Disease and Retinal Degeneration: A Glimpse at Essential Trace Metals in Ocular Fluids and Tissues

2020 ◽  
Vol 16 (12) ◽  
pp. 1073-1083 ◽  
Author(s):  
Alessandra Micera ◽  
Luca Bruno ◽  
Andrea Cacciamani ◽  
Mauro Rongioletti ◽  
Rosanna Squitti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Trace Metals ◽  
Late Onset ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Retinal Disease ◽  
Cellular Aging ◽  
Research Strategies ◽  
Aged People

Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Method: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1802
Author(s):  
Enrique Armijo ◽  
George Edwards ◽  
Andrea Flores ◽  
Jorge Vera ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cerebral Atrophy ◽  
Brain Inflammation ◽  
Neural Precursors ◽  
Model Of Alzheimer’S Disease ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

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