Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

Borghesani, Valentina; Battistella, Giovanni; Mandelli, Maria Luisa; Welch, Ariane E.; Weis, Elizabeth; Younes, Kyan; Neuhaus, John; Grinberg, Lea T.; Ww, Seeley; Spina, Salvatore; Miller, Bruce L.; Miller, Zachary A.; Gorno-Tempini, Maria-Luisa

doi:10.1016/j.nicl.2020.102369

Cited by 41 publications

(52 citation statements)

References 115 publications

(95 reference statements)

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“…In contrast to the previous argument, Borghesani et al, (2020) suggested that the left and the right temporal variant of FTD should be considered the same disease based on their similar neuroanatomical progression patterns within the temporal and contralateral temporal regions[ 50 ]. However, the limitation of that study is that only subjects with TDP type C pathology were included, thereby potentially excluding other underlying pathologies with a different progression pattern.…”

Section: Discussionmentioning

confidence: 99%

“…However, the limitation of that study is that only subjects with TDP type C pathology were included, thereby potentially excluding other underlying pathologies with a different progression pattern. Additionally, it must be noted that most neuropathological studies taking into account the underlying neuropathology of rtvFTD were based on svPPA cohorts[ 20 , 50 ], hence reports of underlying pathology of rtvFTD diagnosed with bvFTD are lacking.…”

Section: Discussionmentioning

confidence: 99%

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Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review

Ulugut

Dijkstra

Scarioni

et al. 2021

acta neuropathol commun

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Although the right temporal variant frontotemporal dementia (rtvFTD) is characterised by distinct clinical and radiological features, its underlying histopathology remains elusive. Being considered a right-sided variant of semantic variant primary progressive aphasia (svPPA), TDP-43 type C pathology has been linked to the syndrome, but this has not been studied in detail in large cohorts. In this case report and systematic review, we report the autopsy results of five subjects diagnosed with rtvFTD from our cohort and 44 single rtvFTD subjects from the literature. Macroscopic pathological evaluation of the combined results revealed that rtvFTD demonstrated either a frontotemporal or temporal evolution, even if the degeneration started in the right temporal lobe initially. FTLD-TDP type C was the most common underlying pathology in rtvFTD, however, in 64% of rtvFTD, other underlying pathologies than FTLD-TDP type C were present, such as Tau-MAPT and FTLD-TDP type A and B. Additionally, accompanying motor neuron or corticospinal tract degeneration was observed in 28% of rtvFTD patients. Our results show that in contrast to the general assumption, rtvFTD might not be a pure FTLD-TDP type C disorder, unlike its left temporal counterpart svPPA. Large sample size pathological studies are warranted to understand the diverse pathologies of the right and left temporal variants of frontotemporal dementia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review

Ulugut

Dijkstra

Scarioni

et al. 2021

acta neuropathol commun

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“…Neuroimaging studies additionally support the notion of ALS and FTD as a continuum showing that motor cortex and anterior cingulate as well as their underlying white matter tracts are impacted in ALS patients, while widespread frontal, anterior cingulate, insular, and temporal lobes are impacted in ALS-FTD and bvFTD patients (Lillo et al, 2012;Crespi et al, 2018;Trojsi et al, 2018;Seeley, 2019;Vinceti et al, 2019). Furthermore, while most forms of ALS are due to pathological inclusions of TDP-43 (with some exceptions, noted in the next section), about half of all bvFTD (Neumann et al, 2006;Perry et al, 2017), most svPPA (Grossman, 2010;Josephs et al, 2011;Borghesani et al, 2020), and a portion of nfvPPA cases are due to TDP-43 (Adams-Carr et al, 2020). The other half of bvFTD, a small minority to few svPPA, over half of nfvPPA, CBS, and PSPS result from underlying tau pathology (Josephs et al, 2011).…”

Section: Clinical Phenotypes Of Ftd and Alsmentioning

confidence: 96%

Moving Toward Patient-Tailored Treatment in ALS and FTD: The Potential of Genomic Assessment as a Tool for Biological Discovery and Trial Recruitment

2021

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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating and intertwined neurodegenerative diseases. Historically, ALS and FTD were considered distinct disorders given differences in presenting clinical symptoms, disease duration, and predicted risk of developing each disease. However, research over recent years has highlighted the considerable clinical, pathological, and genetic overlap of ALS and FTD, and these two syndromes are now thought to represent different manifestations of the same neuropathological disease spectrum. In this review, we discuss the need to shift our focus from studying ALS and FTD in isolation to identifying the biological mechanisms that drive these diseases—both common and distinct—to improve treatment discovery and therapeutic development success. We also emphasize the importance of genomic data to facilitate a “precision medicine” approach for treating ALS and FTD.

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“…The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (59, 13 (13,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) FTLD-tau Pick's type 2, (10%) Absent 52 (52,(51)(52)(53) 5 (5,(4)(5)(6) FTLD-TDP-Type-B with MND 1, (5%) Absent 55 9…”

Section: Data Availabilitymentioning

confidence: 99%

“…[5][6][7][8][9] ATL degeneration is typically caused by FTLD-TDP type C and results in a variety of language, behavioral, and emotional symptoms over the course of the illness. Early ATL degeneration is often asymmetric, 10,11 with focal atrophy of either the left ATL (lATL) or right ATL (rATL). Degeneration soon spreads to the opposite hemisphere, and the clinical symptoms that accompany right-and left-predominant syndromes, therefore, often converge over time.…”

Section: Introductionmentioning

confidence: 99%

Right Anterior Temporal Degeneration, Emotions, and Loss of Nonverbal Semantics: The Emotional Semantic Variant Frontotemporal Dementia

Younes

Borghesani

Montembeault

et al. 2021

Preprint

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Anterior temporal lobe (ATL) degeneration is caused by a pathological process that has a focal onset in the left or right hemisphere. Patients with left-lateralized ATL atrophy typically meet criteria for semantic variant primary progressive aphasia (PPA), a clinical syndrome characterized by loss of verbal semantic knowledge. There is less consensus regarding the symptoms that emerge when atrophy targets the right ATL (rATL), but previous studies have emphasized prosopagnosia as well as alterations in emotion, memory, behavior, and semantic knowledge, symptoms that often lead to a diagnosis of behavioral variant frontotemporal dementia (bvFTD). The goal of the present study was to characterize the cognitive and socioemotional deficits of patients with rATL degeneration in order to refine current conceptualizations of the rATL clinical syndrome. We identified individuals clinically diagnosed as bvFTD or PPA in our cohort of patients prospectively evaluated for FTD-spectrum disorders. We selected patients who also underwent structural MRI and a comprehensive, multidisciplinary evaluation (n = 478). Based on structural MRI atrophy index, individuals with predominant, rATL atrophy (n = 46) were identified and patients with co-occurrence of significant frontal atrophy were excluded. Nineteen patients with rATL degeneration had undergone autopsy. We used the clinical histories to identify early symptoms and examined the cognitive, socioemotional, genetic, and pathological profiles of patients with rATL degeneration. In patients with rATL degeneration, the most common early clinical symptoms were loss of empathy (27%), person-specific semantic knowledge (23%), and complex compulsions (18%). On socioemotional testing and informant-reported measures, patients exhibited diminished interpersonal warmth, empathy, and emotional theory of mind. Neuropsychological testing revealed deficits in identifying famous people and discriminating facial affect despite preserved face perception. FTLD-TDP was the most frequent pathological correlate of rATL degeneration (84%), followed by Pick type (10%), a subtype of FTLD-tau. Our results indicate that patients with early, rATL-predominant degeneration present with a behavioral syndrome that results from loss of empathy for others. The underlying mechanism is a progressive loss of semantic knowledge for concepts of social-emotional relevance. We herein refer to this syndrome as emotional semantic variant frontotemporal dementia. We propose novel diagnostic criteria for this rATL syndrome in order to facilitate early identification in clinical and research settings. This classification is relevant because, if appropriately diagnosed, these patients most often have FTLD-TDP Type-C pathology.

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Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

Cited by 41 publications

References 115 publications

Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review

Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review

Moving Toward Patient-Tailored Treatment in ALS and FTD: The Potential of Genomic Assessment as a Tool for Biological Discovery and Trial Recruitment

Right Anterior Temporal Degeneration, Emotions, and Loss of Nonverbal Semantics: The Emotional Semantic Variant Frontotemporal Dementia

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