Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients

Kim, Hee Jin; Park, Seongbeom; Park, Yu Hyun; Choe, Yeongsim; Cho, Hanna; Lyoo, Chul Hyoung; Yoon, Uicheul; Lee, Jin San; Kim, Yeshin; Kim, Seungjoo; Kim, Jun Pyo; Jung, Young Hee; Ryu, Young Hoon; Choi, Jae Yong; Moon, Seung Hwan; Seong, Joon Kyung; DeCarli, Charles; Weiner, Michael W.; Lockhart, Samuel N.; Cho, Soo Hyun; Na, Duk L.; Seo, Sang Won

doi:10.1007/s00259-019-04498-y

Cited by 21 publications

(20 citation statements)

References 42 publications

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“…The observation that approximately one-third of cognitively normal older adults have AD pathology in their brains has been approved by previous amyloid imaging [18][19][20] and neuropathological studies [21,22]. Similar distributions were found in studies of Asian populations [23][24][25]. Therefore, the cutoff values to define abnormal CSF core biomarkers were < 115.1 pg/ml (lower onethird) for Aβ 1-42 , > 40.05 pg/ml (upper one-third) for P-tau, and > 187.32 pg/ml (upper one-third) for T-tau, respectively Aggregated tau and neurodegeneration groups were merged to reduce the number of groups to be compared, which resulted in four different biomarker group combinations, including stage 0, stage 1, stage 2, and suspected non-AD pathology (SNAP).…”

Section: Discussionsupporting

confidence: 52%

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Tan

et al. 2020

Mol Neurodegeneration

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Background: Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD). Whether TREM2 levels are pathologically altered during the preclinical phase, and whether cerebrospinal fluid (CSF) soluble TREM2 protein (sTREM2) has a relationship with major pathological processes including Aβ and tau deposition are still unclear.Methods: According to the NIA-AA criteria, 659 cognitively normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups, stage 0 (normal Aβ 1-42 , T-tau and P-tau), stage 1 (low Aβ 1-42 , normal T-tau and P-tau), stage 2 (low Aβ 1-42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ 1-42 and high T-tau or P-tau), to examine changes of CSF sTREM2 in the preclinical AD. Biomarker cut-off was based on the assumption that one-third of adults with normal cognition have AD pathology.Results: The level of CSF sTREM2 in the stage 1 decreased compared with the stage 0 (P < 0.001), and then increased in the stage 2 (P = 0.008). SNAP individuals also had significantly increased CSF sTREM2 (P < 0.001). Results of multiple linear regressions also showed positive correlations of CSF sTREM2 with Aβ 1-42 (β = 0.192, P < 0.001), T-tau (β = 0.215, P < 0.001) and P-tau (β = 0.123, P < 0.001).Conclusion: CSF sTREM2 levels are dynamic in preclinical AD. Aβ pathology is associated with a decrease in CSF sTREM2 in the absence of tau deposition and neurodegeneration. However, tau pathology and neurodegeneration are associated with an increase in CSF sTREM2.

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Section: Discussionsupporting

confidence: 52%

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Tan

et al. 2020

Mol Neurodegeneration

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“…In addition to older adults who were cognitively unimpaired or diagnosed with mild cognitive impairment, many studies included individuals diagnosed with dementia. While the majority of studies recruited participants with probable AD, other dementia syndromes included AD variants (i.e., dysexecutive AD, posterior cortical atrophy; [ 14 , 36 ]), hippocampal sclerosis [ 19 ], subcortical vascular cognitive impairment [ 26 ], and non-AD neurodegenerative disorders (e.g., Lewy body dementia, primary progressive aphasia; [ 34 ]). The current review also included one study investigating AD in individuals with Down syndrome [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

What’s the cut-point?: a systematic investigation of tau PET thresholding methods

et al. 2022

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Background Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer’s disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity. Methods First, a literature search was conducted in PubMed to identify studies of AD and related clinical phenotypes that used the Flortaucipir (AV-1451) tau PET tracer to derive a binary cut-point for tau positivity. Of 540 articles screened and 47 full-texts reviewed, 23 cohort studies met inclusion criteria with a total of 6536 participants. Second, we derived and compared tau PET cut-points in a 2 × 2 × 2 design that systematically varied region (temporal meta-ROI and entorhinal cortex), analytic method (receiver operating characteristics and 2 standard deviations above comparison group), and criterion/comparison variable (amyloid-beta negative cognitively unimpaired or cognitively unimpaired only) using a sample of 453 older adults from the Alzheimer’s Disease Neuroimaging Initiative. Results For the systematic review, notable variability in sample characteristics, preprocessing methods, region of interest, and analytic approach were observed, which were accompanied by discrepancy in proposed tau PET cut points. The empirical follow-up indicated the cut-point derived based on 2 standard deviations above a either comparison group in either ROI best differentiated tau positive and negative groups on cerebrospinal fluid phosphorylated tau, Mini-Mental State Examination score, and delayed memory performance. Conclusions Given the impact of discrepant thresholds on tau positivity rates, biomarker staging, and eligibility for future clinical treatment trials, recommendations are offered to select cut-point derivations based on the unique goals and priorities of different studies.

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“…In terms of the tau marker, it has been shown that tau positivity is 70% (14/20) in Aβ (+) ADCI patients, 25.9% (7/27) in Aβ (+) SVCI patients, and 6.1% (2/33) in Aβ (−) SVCI patients. [ 52 ].…”

Section: Imaging Markers Of Alzheimer’s Disease (Ad) and Cerebral Sma...mentioning

confidence: 99%

“…SVCI patients show distinct brain structural and cognitive trajectories based on AT (Aβ/tau) biomarker profiles [ 52 ]. A previous study showed that patients in the A+T+ group predicted a more rapid decline in structural and cognitive trajectories than those in the A+T− group, followed by those in the A−T− group [ 52 ]. Moreover, AD markers and CSVD burden have a synergistic effect on cognitive decline.…”

Section: Imaging Markers Of Alzheimer’s Disease (Ad) and Cerebral Sma...mentioning

confidence: 99%

Interaction between Alzheimer’s Disease and Cerebral Small Vessel Disease: A Review Focused on Neuroimaging Markers

Kim

Weiner

et al. 2022

IJMS

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Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) and tau, and subcortical vascular cognitive impairment (SVCI) is characterized by cerebral small vessel disease (CSVD). They are the most common causes of cognitive impairment in the elderly population. Concurrent CSVD burden is more commonly observed in AD-type dementia than in other neurodegenerative diseases. Recent developments in Aβ and tau positron emission tomography (PET) have enabled the investigation of the relationship between AD biomarkers and CSVD in vivo. In this review, we focus on the interaction between AD and CSVD markers and the clinical effects of these two markers based on molecular imaging studies. First, we cover the frequency of AD imaging markers, including Aβ and tau, in patients with SVCI. Second, we discuss the relationship between AD and CSVD markers and the potential distinct pathobiology of AD markers in SVCI compared to AD-type dementia. Next, we discuss the clinical effects of AD and CSVD markers in SVCI, and hemorrhagic markers in cerebral amyloid angiopathy. Finally, this review provides both the current challenges and future perspectives for SVCI.

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Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients

Cited by 21 publications

References 42 publications

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

What’s the cut-point?: a systematic investigation of tau PET thresholding methods

Interaction between Alzheimer’s Disease and Cerebral Small Vessel Disease: A Review Focused on Neuroimaging Markers

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