A Comparative Study of Site-Specific Distribution of Aging-Related Tau Astrogliopathy and Its Risk Factors Between Alzheimer Disease and Cognitive Healthy Brains: The Hisayama Study

2021 ◽  
Author(s):  
Kaoru Yagita ◽  
Hiroyuki Honda ◽  
Tomoyuki Ohara ◽  
Hideomi Hamasaki ◽  
Sachiko Koyama ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Neurofibrillary Tangle ◽  
Olfactory Nerve ◽  
Braak Stage ◽  
Age At Death ◽  
Healthy Elderly ◽  
Age Related ◽  
Specific Distribution ◽  
Japanese General Population ◽  
Semiquantitative Evaluation

Abstract Knowledge of aging-related tau astrogliopathy (ARTAG) in healthy elderly individuals remains incomplete and studies to date have not focused on the olfactory nerve, which is a vulnerable site of various neurodegenerative disease pathologies. We performed a semiquantitative evaluation of ARTAG in 110 autopsies in the Japanese general population (Hisayama study). Our analysis focused on Alzheimer disease (AD) and cognitive healthy cases (HC), including primary age-related tauopathy. Among the various diseased and nondiseased brains, ARTAG was frequently observed in the amygdala. The ARTAG of HC was exclusively limited to the amygdala whereas gray matter ARTAG in AD cases was prominent in the putamen and middle frontal gyrus following the amygdala. ARTAG of the olfactory nerve mainly consists of subpial pathology that was milder in the amygdala. A logistic regression analysis revealed that age at death and neurofibrillary tangle Braak stage significantly affected the ARTAG of HC. In AD, age at death and male gender had significant effects on ARTAG. In addition, the Thal phase significantly affected the presence of white matter ARTAG. In conclusion, our research revealed differences in the distribution of ARTAG and affected variables across AD and HC individuals.

scholarly journals Alzheimer risk loci and associated neuropathology in a population-based study (Vantaa 85+)

2018 ◽  
Vol 4 (1) ◽  
pp. e211 ◽  
Author(s):  
Mira Mäkelä ◽  
Karri Kaivola ◽  
Miko Valori ◽  
Anders Paetau ◽  
Tuomo Polvikoski ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Association Studies ◽  
Neurofibrillary Tangle ◽  
Snp Array ◽  
Population Based ◽  
Continuous Variable ◽  
Amyloid Angiopathy ◽  
Braak Stage ◽  
Genome Wide Association Studies ◽  
Population Based Study

ObjectiveTo test the association of distinct neuropathologic features of Alzheimer disease (AD) with risk loci identified in genome-wide association studies.MethodsVantaa 85+ is a population-based study that includes 601 participants aged ≥85 years, of which 256 were neuropathologically examined. We analyzed 29 AD risk loci in addition to APOE ε4, which was studied separately and used as a covariate. Genotyping was performed using a single nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038 variants). Participants with Consortium to Establish a Registry for Alzheimer Disease (CERAD) (neuritic Aβ plaques) scores 0 (n = 65) vs score M + F (n = 171) and Braak (neurofibrillary tangle pathology) stages 0–II (n = 74) vs stages IV–VI (n = 119), and with capillary Aβ (CapAβ, n = 77) vs without (n = 179) were compared. Cerebral amyloid angiopathy (CAA) percentage was analyzed as a continuous variable.ResultsAltogether, 24 of the 29 loci were associated (at p < 0.05) with one or more AD-related neuropathologic features in either SNP array or imputation data. Fifteen loci associated with CERAD score, smallest p = 0.0002122, odds ratio (OR) 2.67 (1.58–4.49) at MEF2C locus. Fifteen loci associated with Braak stage, smallest p = 0.004372, OR 0.31 (0.14–0.69) at GAB2 locus. Twenty loci associated with CAA, smallest p = 7.17E-07, β 14.4 (8.88–20) at CR1 locus. Fifteen loci associated with CapAβ smallest p = 0.002594, OR 0.54 (0.37–0.81) at HLA-DRB1 locus. Certain loci associated with specific neuropathologic features. CASS4, CLU, and ZCWPW1 associated only with CAA, while TREM2 and HLA-DRB5 associated only with CapAβ.ConclusionsAD risk loci differ in their association with neuropathologic features, and we show for the first time distinct risk loci for CAA and CapAβ.

scholarly journals Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study

2021 ◽  
Author(s):  
Megan A Iida ◽  
Kurt Farrell ◽  
Jamie M Walker ◽  
Timothy E Richardson ◽  
Gabe Marx ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Brain Regions ◽  
Braak Stage ◽  
Autopsy Study ◽  
Factors Affecting ◽  
Braak Staging ◽  
Age Related

Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n=174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p=0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p=0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p<0.0001), but other features including ARTAG (p=0.03) and hippocampal atrophy (p=0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.

scholarly journals Comparison of symptomatic and asymptomatic persons with primary age-related tauopathy

Neurology ◽  
2017 ◽  
Vol 89 (16) ◽  
pp. 1707-1715 ◽  
Author(s):  
Lilah M. Besser ◽  
John F. Crary ◽  
Charles Mock ◽  
Walter A. Kukull
Keyword(s):  
Neurofibrillary Tangle ◽  
Amyloid Plaques ◽  
Amyloid Angiopathy ◽  
Braak Stage ◽  
Neuritic Plaques ◽  
Clinical Dementia Rating ◽  
Factors Associated ◽  
Clinicopathologic Study ◽  
Age Related ◽  
History Of

Objective:To conduct a clinicopathologic study to characterize clinical and neuropathologic features associated with cognitive impairment in participants with no neuritic amyloid plaques (primary age-related tauopathy [PART] definite) and sparse neuritic plaques (amyloid sparse).Methods:Using the National Alzheimer's Coordinating Center database, we identified 377 individuals who were PART definite (n = 170) or amyloid sparse (n = 207), clinically examined within 1 year of death, and autopsied at 1 of 26 National Institute on Aging–funded Alzheimer's Disease Centers. Factors associated with the odds of being symptomatic (global Clinical Dementia Rating [CDR] score >0) were identified with multivariable logistic regression.Results:PART-definite participants less often had a high Braak neurofibrillary tangle stage V or VI (4%) compared to amyloid sparse participants (28%, p < 0.001). Of the PART-definite participants, 98 were symptomatic and 72 asymptomatic according to their global CDR scores. PART-definite participants were less often symptomatic (58%) compared with amyloid sparse participants (80%, p < 0.001). Within the PART-definite group, independent predictors of symptomatic status included depression (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 2.15–8.19), Braak stage (aOR 1.42, 95% CI 1.04–1.95), and history of stroke (aOR 8.09, 95% CI 2.63–24.82). Within the amyloid sparse group, independent predictors of symptomatic status included education (aOR 0.80, 95% CI 0.65–0.99), Braak stage (aOR 1.91, 95% CI 1.07–3.43), and amyloid angiopathy (aOR 2.75, 95% CI 1.14–6.64).Conclusions:These findings support the hypothesis that participants with PART have an amyloid-independent dementing Alzheimer disease–like temporal lobe tauopathy.

Asymmetry of Hippocampal Tau Pathology in Primary Age-Related Tauopathy and Alzheimer Disease

2021 ◽  
Author(s):  
Jamie M Walker ◽  
Yelena Fudym ◽  
Kurt Farrell ◽  
Megan A Iida ◽  
Kevin F Bieniek ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Neurofibrillary Degeneration ◽  
Temporal Region ◽  
Braak Stage ◽  
Neuritic Plaques ◽  
Tau Pathology ◽  
Age Related ◽  
Significant Difference ◽  
Left And Right ◽  
The Right

Abstract Primary age-related tauopathy (PART) is a neurodegenerative entity defined as neurofibrillary degeneration generally restricted to the medial temporal region (Braak stage I–IV) with complete or near absence of diffuse and neuritic plaques. Symptoms range in severity but are generally milder and later in onset than in Alzheimer disease (AD). Recently, an early predilection for neurofibrillary degeneration in the hippocampal CA2 subregion has been demonstrated in PART, whereas AD neuropathologic change (ADNC) typically displays relative sparing of CA2 until later stages. In this study, we utilized a semiquantitative scoring system to evaluate asymmetry of neurofibrillary degeneration between left and right hippocampi in 67 PART cases and 17 ADNC cases. 49% of PART cases demonstrated asymmetric findings in at least one hippocampal subregion, and 79% of the asymmetric cases displayed some degree of CA2 asymmetry. Additionally, 19% of cases revealed a difference in Braak score between the right and left hippocampi. There was a significant difference in CA2 neurofibrillary degeneration (p = 0.0006) and CA2/CA1 ratio (p &lt; 0.0001) when comparing the contralateral sides, but neither right nor left was more consistently affected. These data show the importance of analyzing bilateral hippocampi in the diagnostic evaluation of PART and potentially of other neurodegenerative diseases.

scholarly journals Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Megan A. Iida ◽  
Kurt Farrell ◽  
Jamie M. Walker ◽  
Timothy E. Richardson ◽  
Gabriel A. Marx ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Brain Regions ◽  
Braak Stage ◽  
Autopsy Study ◽  
Factors Affecting ◽  
Braak Staging ◽  
Age Related

AbstractPrimary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n = 174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p = 0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p = 0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p < 0.0001), but other features including ARTAG (p = 0.03) and hippocampal atrophy (p = 0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Effect of the Interaction Between Hypertension and Cerebral White Matter Changes on the Progression of Alzheimer Disease

2018 ◽  
Vol 15 (14) ◽  
pp. 1354-1360 ◽  
Author(s):  
Ping-Song Chou ◽  
Yi-Hui Kao ◽  
Meng-Ni Wu ◽  
Mei-Chuan Chou ◽  
Chun-Hung Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Alzheimer Disease ◽  
Rating Scale ◽  
Vital Role ◽  
Independent Effect ◽  
Cerebral White Matter ◽  
Clinical Dementia Rating ◽  
White Matter Changes ◽  
Age Related ◽  
The Mean

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

scholarly journals Perilla Seed Oil Enhances Cognitive Function and Mental Health in Healthy Elderly Japanese Individuals by Enhancing the Biological Antioxidant Potential

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1130
Author(s):  
Michio Hashimoto ◽  
Kentaro Matsuzaki ◽  
Shahdat Hossain ◽  
Tomoko Ito ◽  
Harumi Wakatsuki ◽  
...  
Keyword(s):  
Mental Health ◽  
Cognitive Function ◽  
Plasma Membranes ◽  
Seed Oil ◽  
Antioxidant Potential ◽  
Control Group ◽  
Healthy Elderly ◽  
Age Related ◽  
Elderly Japanese ◽  
Perilla Seed

Oxidative stress plays an important role in age-associated cognitive decline. We recently reported that dietary intake of perilla seed oil (PO), a rich source of α-linolenic acid (LNA, C18:3, ω-3), helps in maintaining good mental health in adults. This study aimed to investigate the impacts of dietary PO intake on cognitive functions and mental health in healthy, elderly Japanese individuals. Seventy-five healthy volunteers aged 64–84 years were randomly divided into two groups: a control group and a PO-administered group. At baseline and at 12 months of intervention, cognitive function, mental health condition, fatty acid profile of the red blood cell plasma membranes (RBC-PM), and serum biochemical parameters were evaluated. Results showed that serum biological antioxidant potential and LNA levels in the RBC-PM at 12 months after the trial were significantly higher in the PO group compared to the control group. Further, both the cognitive function measures, as evaluated by the Frontal Assessment Battery test and the apathy scores, tended to be improved after 12 months in the PO group. Our results demonstrate that dietary PO intake enhances the antioxidant potential and prevents the age-related cognitive and mental decline in healthy elderly individuals by enhancing the blood LNA levels.

scholarly journals Visual Attention and Aging: an Age-Related Cognitive Model of Positive Adaptation

2014 ◽  
Vol 4 (3) ◽  
pp. 181-191
Author(s):  
José Manuel Rodríguez-Ferrer
Keyword(s):  
Young People ◽  
Visual Attention ◽  
Response Times ◽  
Age Groups ◽  
Cognitive Model ◽  
Covert Attention ◽  
Positive Adaptation ◽  
Healthy Elderly ◽  
Age Related ◽  
Healthy Young People

We have studied the effects of normal aging on visual attention. Have participated a group of 38 healthy elderly people with an average age of 67.8 years and a group of 39 healthy young people with average age of 19.2 years. In a first experiment of visual detection, response times were recorded, with and without covert attention, to the presentation of stimuli (0.5º in diameter grey circles) appearing in three eccentricities (2.15, 3.83 and 5.53° of visual field) and with three levels of contrast (6, 16 and 78%). In a second experiment of visual form discrimination circles and squares with the same features as in the previous experiment were presented, but in this case subjects only should respond to the emergence of the circles. In both age groups, the covert attention reduced response times. Compared to young people, the older group achieved better results in some aspects of attention tests and response times were reduced more in the stimuli of greater eccentricity. The data suggest that there is a mechanism of adaptation in aging, in which visual attention especially favors the perception of those stimuli more difficult to detec

Sign in / Sign up

Export Citation Format

Share Document