Primary age-related tauopathy in a Chinese cohort

Wang, Xin; Zhang, Lei; Lü, Hui; Wu, Juan-Li; Liang, Huazheng; Lei, Chong; Tao, Qing‐Qing; Wu, Zhi‐Ying; Zhu, Keqing

doi:10.1631/jzus.b1900262

“…The PART cases examined in the current study were 59-89 years old at death, 13 being male and 10 female, and died of various diseases (Table 1). Therefore, in agreement with previous reports (Crary et al, 2014;Kaufman et al, 2018;Kim et al, 2019;Wang et al, 2020), PART is commonly present in the brains of elderly Chinese obtained via community-based brain banking.…”

Section: Discussionsupporting

confidence: 93%

“…This lesion refers to the occurrence of tauopathy in the absence of Aβ deposition. The tauopathy is present primarily in the temporal lobe structures, with its extent ranging from Braak NFT stages I to IV (Kaufman et al, 2018 ; Kim et al, 2019 ; Wang et al, 2020 ). Individuals with PART are cognitively normal to their ages or have mild amnestic symptoms, while a minority could be severely demented (Besser et al, 2017 ; Jefferson-George et al, 2017 ; Quintas-Neves et al, 2019 ; Teylan et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Early Dendritic Dystrophy in Human Brains With Primary Age-Related Tauopathy

Shi

¹

,

Tu

²

,

Jiang

³

et al. 2020

Front. Aging Neurosci.

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Dystrophic neurites (DNs) are found in many neurological conditions such as traumatic brain injury and age-related neurodegenerative diseases. In Alzheimer’s disease (AD) specifically, senile plaques containing silver-stained DNs were already described in the original literature defining this disease. These DNs could be both axonal and dendritic in origin, while axonal dystrophy relative to plaque formation has been more extensively studied. Here, we demonstrate an early occurrence of dendritic dystrophy in the hippocampal CA1 and subicular regions in human brains (n = 23) with primary age-related tauopathy (PART), with neurofibrillary tangle (NFT) burden ranging from Braak stages I to III in the absence of cerebral β-amyloid (Aβ) deposition. In Bielschowsky’s silver stain, segmented fusiform swellings on the apical dendrites of hippocampal and subicular pyramidal neurons were observed in all the cases, primarily over the stratum radiatum (s.r.). The numbers of silver-stained neuronal somata and dendritic swellings counted over CA1 to subiculum were positively correlated among the cases. Swollen dendritic processes were also detected in sections immunolabeled for phosphorylated tau (pTau) and sortilin. In aged and AD brains with both Aβ and pTau pathologies, silver- and immunolabeled dystrophic-like dendritic profiles occurred around and within individual neuritic plaques. These findings implicate that dendritic dystrophy can occur among hippocampal pyramidal neurons in human brains with PART. Therefore, as with the case of axonal dystrophy reported in literature, dendritic dystrophy can develop prior to Alzheimer-type plaque and tangle formation in the human brain.

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“…The authors declared no conflict of interest. Reply to "Chronic Traumatic Encephalopathy and Primary Age-Related Tauopathy" Jesse Mez, MD, MS , 1,2,3 Daniel H. Daneshvar, MD, PhD, 1,4 Michael L. Alosco, PhD, 1,2 Victor E. Alvarez, MD, 1,5,6 Bertrand R. Huber, MD, PhD, 1,2,5,6 Thor D. Stein, MD, PhD, 1,3,5,6,7 Ann C. McKee 1,2,3,5,6,7 We thank the authors for their interest in our study. 1 Chen and Tao raise several important points regarding the differential diagnosis between chronic traumatic encephalopathy (CTE) and primary age-related tauopathy (PART).…”

Section: Potential Conflicts Of Interestmentioning

confidence: 99%

Chronic Traumatic Encephalopathy and Primary Age‐Related Tauopathy

Chen

¹

,

Tao

²

2020

Annals of Neurology

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It was with great interest that we read the article published by Mez et al who determined the relationship between the duration of football played and chronic traumatic encephalopathy (CTE) risk and severity in 266 deceased American football players. The results showed that the duration of football played had a strong dose-response relationship with CTE neuropathology after accounting for brain bank selection bias. 1 In 2016, preliminary consensus criteria were proposed for defining the neuropathology of CTE and concluded that CTE can be distinguished from other neurodegenerative diseases. However, in recent years, emerging evidence has indicated that the neuropathology described as unique to CTE may not be unique or specific to those who have experienced chronic traumatic brain injury. 2 Considering that the mean age at death of participants in this study was 48.9 to 68.7 years old, we raise one concern-that the effects of primary age-related tauopathy (PART) could be taken into consideration. PART is a common pathology associated with aging and presents pathologically as a non-amyloidbeta tauopathy with features overlapping with CTE. 3 A previous study found initial tau deposition in all individuals aged 40 years or older. 4 Our previous study demonstrated that PART was frequently observed in specimens from a Chinese brain bank. 5 Aging and the microtubule-associated protein tau (MAPT) gene H1 haplotype are the known major risk factors for PART. The relationship between the severity of the pathology and the duration of football played might partly be caused by the different distributions of age and MAPT gene H1 haplotype between the 2 groups if the pathology of some participants is PART rather than CTE. Furthermore, the study did not show a relation between cognitive function and the severity of pathology. Compared with patients with CTE, patients with PART usually have a relatively well-preserved cognitive function, but patients with higher neurofibrillary tangle (NFT) stages are more likely to have mild cognitive impairment (MCI). Cognitive impairment correlates with the severity of pathology in both CTE and PART, but it is more obvious in CTE. Thus, in participants with severe pathology in whom cognitive function is preserved, the diagnosis could favor PART rather than CTE. At present, there is no specific marker to pathologically differentiate CTE from PART. Future research is needed to determine whether patients with CTE suffer from a unique progressive neurodegenerative process, genetic predisposition, specific combinations of neuropathologies (eg, tau immunophenotypes, TDP-43, amyloid-β, synaptic dysfunction, and neuronal loss), and regional distribution patterns of pathologies need to be further evaluated for their roles in distinguishing CTE and PART.

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“…However, PART typically occurs at an advanced age with the vast majority of cases over the age of 80. 7,8 In the Wang et al study, 9 the average age of the patients with PART was 76 years, and only 3 individuals (7%) with PART died in their 50s. Thus, the mean age of the subjects with CTE in our study is far younger than the mean age of subjects with PART.…”

mentioning

confidence: 96%

Reply to “Chronic Traumatic Encephalopathy and Primary Age‐Related Tauopathy”

Mez

¹

,

Daneshvar

²

,

Alosco

³

et al. 2020

Annals of Neurology

View full text Add to dashboard Cite

It was with great interest that we read the article published by Mez et al who determined the relationship between the duration of football played and chronic traumatic encephalopathy (CTE) risk and severity in 266 deceased American football players. The results showed that the duration of football played had a strong dose-response relationship with CTE neuropathology after accounting for brain bank selection bias. 1 In 2016, preliminary consensus criteria were proposed for defining the neuropathology of CTE and concluded that CTE can be distinguished from other neurodegenerative diseases. However, in recent years, emerging evidence has indicated that the neuropathology described as unique to CTE may not be unique or specific to those who have experienced chronic traumatic brain injury. 2 Considering that the mean age at death of participants in this study was 48.9 to 68.7 years old, we raise one concern-that the effects of primary age-related tauopathy (PART) could be taken into consideration. PART is a common pathology associated with aging and presents pathologically as a non-amyloidbeta tauopathy with features overlapping with CTE. 3 A previous study found initial tau deposition in all individuals aged 40 years or older. 4 Our previous study demonstrated that PART was frequently observed in specimens from a Chinese brain bank. 5 Aging and the microtubule-associated protein tau (MAPT) gene H1 haplotype are the known major risk factors for PART. The relationship between the severity of the pathology and the duration of football played might partly be caused by the different distributions of age and MAPT gene H1 haplotype between the 2 groups if the pathology of some participants is PART rather than CTE. Furthermore, the study did not show a relation between cognitive function and the severity of pathology. Compared with patients with CTE, patients with PART usually have a relatively well-preserved cognitive function, but patients with higher neurofibrillary tangle (NFT) stages are more likely to have mild cognitive impairment (MCI). Cognitive impairment correlates with the severity of pathology in both CTE and PART, but it is more obvious in CTE. Thus, in participants with severe pathology in whom cognitive function is preserved, the diagnosis could favor PART rather than CTE. At present, there is no specific marker to pathologically differentiate CTE from PART. Future research is needed to determine whether patients with CTE suffer from a unique progressive neurodegenerative process, genetic predisposition, specific combinations of neuropathologies (eg, tau immunophenotypes, TDP-43, amyloid-β, synaptic dysfunction, and neuronal loss), and regional distribution patterns of pathologies need to be further evaluated for their roles in distinguishing CTE and PART.

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Primary age-related tauopathy in a Chinese cohort

Cited by 4 publications

References 21 publications

Early Dendritic Dystrophy in Human Brains With Primary Age-Related Tauopathy

Early Dendritic Dystrophy in Human Brains With Primary Age-Related Tauopathy

Chronic Traumatic Encephalopathy and Primary Age‐Related Tauopathy

Reply to “Chronic Traumatic Encephalopathy and Primary Age‐Related Tauopathy”

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