Suspected non-Alzheimer's pathology – Is it non-Alzheimer's or non-amyloid?

Dani, Melanie; Brooks, David J.; Edison, Paul

doi:10.1016/j.arr.2017.02.003

Cited by 37 publications

(42 citation statements)

References 96 publications

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“…Studies have consistently estimated the proportion of SNAP individuals to be about 23-25.9% among clinically normal populations [5,37]. Among patients with mild cognitive impairment and AD, SNAP varies between 7-39% [38,39]. In our study, SNAP patients accounted for 56% in a group of mild dementia patients.…”

Section: Discussionsupporting

confidence: 50%

Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

Wong

Yong

Lim

et al. 2019

JAD

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Background: Non-amyloid mechanisms behind neurodegeneration and cognition impairment are unclear. Cerebrovascular disease (CVD) may play an important role in suspected non-Alzheimer's pathophysiology (SNAP), especially in Asia. Objective: To examine the association between CVD and medial temporal lobe atrophy (MTA) in amyloid-␤ negative patients with mild amnestic type dementia. Methods: Thirty-six mild dementia patients with complete neuropsychological, cerebrospinal fluid (CSF) biomarker, and neuroimaging information were included. Only patients with clinically significant MTA were recruited. Patients were categorized based on their CSF A␤ levels. Neuroimaging and neuropsychological variables were analyzed. Results: Despite comparable MTA between A␤ positive and negative patients, A␤-negative patients had significantly greater white matter hyperintensities (WMH; Total Fazekas Rating) than their A␤-positive counterparts (6.42 versus 4.19, p = 0.03). A larger proportion of A␤-negative patients also had severe and confluent WMH. Regression analyses controlling for baseline characteristics yielded consistent results. Conclusion: Our findings demonstrate that MTA is associated with greater CVD burden among A␤-negative patients with amnestic type dementia. CVD may be an important mechanism behind hippocampal atrophy. This has implications on clinical management strategies, where measures to reduce CVD may slow neurodegeneration and disease progression.

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Section: Discussionsupporting

confidence: 50%

Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

Wong

Yong

Lim

et al. 2019

JAD

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“…On the contrary, the “A+TN−” biomarker profiles had the lowest CSF PGRN. We next grouped the subjects that fall into each of the biomarker category of “suspected non‐Alzheimer's pathophysiology” (SNAP; Table , highlighted in dark grey) (Jack et al , , ; Caroli et al , ; Dani et al , ) and we compared them to the healthy controls and the Alzheimer's continuum category as a whole. CSF PGRN significantly differ between categories ( F 2,778 = 24.7, P < 0.0001, Fig EV1B), and Bonferroni corrected pair‐wise post hoc tests showed that CSF PGRN was significantly higher in the SNAP category compared to the healthy controls ( P < 0.0001) and Alzheimer's continuum categories ( P < 0.0001).…”

Section: Resultsmentioning

confidence: 99%

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline

et al. 2018

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Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospinal fluid (CSF) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease.

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“…5,48,82,83,85 The cornerstone for such characterization includes the absence of detectable cerebral amyloid levels by amyloid PET or CSF analyses. 5,47,48,85,[90][91][92][93] Such cases, however, may also comprise a host of other degenerative disease states, including vascular dementia, DLB, FTD, hippocampal sclerosis of aging, and argyrophilic grain disease. Exclusion of subjects with DLB or FTD phenotypes and of subjects with vascular dementia based on clinical and imaging evidence of cerebrovascular disease leads to increased specificity for PART.…”

Section: Imaging and Fluid Biomarkersmentioning

confidence: 99%

“…94 Additionally, biochemical analyses of CSF tau levels can help identify phosphorylated species and mixed tau isoform composition that could reliably predict PART. 5,45,47,[54][55][56][57]67,93 Prospective testing of such multimodal use of antemortem biomarkers remains to be confirmed but holds much promise for the antemortem detection of pathologic diseases such as PART. 48,90 Genetics Given the arguable overlap between PART and AD, links between the known genetic associations in AD have been explored in PART.…”

Section: Imaging and Fluid Biomarkersmentioning

confidence: 99%

Hippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy

Jicha¹,

Nelson²

2019

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEW: Hippocampal sclerosis, argyrophilic grain disease, and primary age-related tauopathy are common Alzheimer disease mimics that currently lack clinical diagnostic criteria. Increased understanding of these pathologic entities is important for the neurologist who may encounter patients with an unusually slowly progressive degenerative dementia that may appear to meet criteria for Alzheimer disease but who progress to develop symptoms that are unusual for classic Alzheimer disease RECENT FINDINGS: Hippocampal sclerosis has traditionally been associated with hypoxic/ischemic injury and poorly controlled epilepsy, but it is now recognized that hippocampal sclerosis may also be associated with a unique degenerative disease of aging or may be an associated pathologic finding in many cases of frontotemporal lobar degeneration. Argyrophilic grain disease has been recognized as an enigma in the field of pathology for over 30 years, but recent discoveries suggest that it may overlap with other tau-related disorders within the spectrum of frontotemporal lobar degeneration. Primary age-related tauopathy has long been recognized as a distinct clinical entity that lies on the Alzheimer pathologic spectrum, with the presence of neurofibrillary tangles that lack the coexistent Alzheimer plaque development; thus, it is thought to represent a distinct pathologic entity. SUMMARY: Despite advances in dementia diagnosis that suggest that we have identified and unlocked the mysteries of the major degenerative disease states responsible for cognitive decline and dementia in the elderly, diseases such as hippocampal sclerosis, argyrophilic grain disease, and primary age-related tauopathy demonstrate that we remain on the frontier of discovery and that our diagnostic repertoire of diseases responsible for such clinical symptoms remains in its infancy. Understanding such diagnostic confounds is important for the neurologist in assigning appropriate diagnoses and selecting appropriate therapeutic management strategies for patients with mild cognitive impairment and dementia. 208

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Suspected non-Alzheimer's pathology – Is it non-Alzheimer's or non-amyloid?

Cited by 37 publications

References 96 publications

Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline

Hippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy

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