Relation of plasma <i>β</i>‐amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study

Romero, José R.; Demissie, Serkalem; Beiser, Alexa S.; Himali, Jayandra J.; DeCarli, Charles; Levy, Daniel; Seshadri, Sudha

doi:10.1002/acn3.51066

Cited by 21 publications

(16 citation statements)

References 26 publications

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“…Using cerebrospinal fluid may have had a higher predictive value [ 57 , 116 , 117 , 118 ]. Elevations in serum NF-L levels were reported inconsistently in studies plagued with small fibers, unadjusted for comorbidities, or limited to the most sick patients [ 12 , 32 , 35 , 94 , 119 , 120 , 121 ]. Gisslen et al reported the normalization of GFAP and NF-L six months after the resolution of COVID-19, but their patients continued to exhibit neurological symptoms and their study was limited to these markers [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Gisslen et al reported the normalization of GFAP and NF-L six months after the resolution of COVID-19, but their patients continued to exhibit neurological symptoms and their study was limited to these markers [ 34 ]. Persistent elevations of several neurodegeneration markers suggest an ongoing pathological process in COVID survivors that is heterogeneous [ 38 , 43 , 44 , 46 , 51 , 52 , 55 , 87 , 94 , 111 , 122 ]. This indicates a potential mechanism for post-COVID-19 cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

“…The persistent elevations of markers is accompanied by decreases in somre neuroprotective molecules during acute COVID-19 admission with some recovery afterwards [ 85 , 134 , 135 ]. Clusterin, TREM-2 and fetuin are linked to neuronal protection and cleavage of several pathological proteins [ 48 , 85 , 86 , 94 , 136 , 137 ]. The changes in their respective serum levels has been demonstrated in several inflammatory processes and is linked to the severity of the inflammatory response [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

“…Clusterin, fetuin-A, and TREM-2 are examples of biomarkers linked to delays in the progression of neurodegeneration [ 86 , 91 , 92 , 93 ]. The depletion of these factors results in the progression of neurodegenerative disorders and excess cerebrovascular strokes [ 85 , 86 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. Apolipoprotein E (apoE) was frequently linked to dementia progression in general, but in COVID-19, this factor may be of particular importance [ 98 ].…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes

et al. 2021

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The balance between neurodegeneration, neuroinflammation, neuroprotection, and COVID-19-directed therapy may underly the heterogeneity of SARS-CoV-2′s neurological outcomes. A total of 105 patients hospitalized with a diagnosis of COVID-19 had serum collected over a 6 month period to assess neuroinflammatory (MIF, CCL23, MCP-1), neuro-injury (NFL, NCAM-1), neurodegenerative (KLK6, τ, phospho τ, amyloids, TDP43, YKL40), and neuroprotective (clusterin, fetuin, TREM-2) proteins. These were compared to markers of nonspecific inflammatory responses (IL-6, D-dimer, CRP) and of the overall viral burden (spike protein). Data regarding treatment (steroids, convalescent plasma, remdasavir), pre-existing conditions, and incidences of strokes were collected. Amyloid β42, TDP43, NF-L, and KLK6 serum levels declined 2–3 days post-admission, yet recovered to admission baseline levels by 7 days. YKL-40 and NCAM-1 levels remained elevated over time, with clusters of differential responses identified among TREM-2, TDP43, and YKL40. Fetuin was elevated after the onset of COVID-19 while TREM-2 initially declined before significantly increasing over time. MIF serum level was increased 3–7 days after admission. Ferritin correlated with TDP-43 and KLK6. No treatment with remdesivir coincided with elevations in Amyloid-β40. A lack of convalescent plasma resulted in increased NCAM-1 and total tau, and steroidal treatments did not significantly affect any markers. A total of 11 incidences of stroke were registered up to six months after initial admission for COVID-19. Elevated D-dimer, platelet counts, IL-6, and leukopenia were observed. Variable MIF serum levels differentiated patients with CVA from those who did not have a stroke during the acute phase of COVID-19. This study demonstrated concomitant and opposite changes in neurodegenerative and neuroprotective markers persisting well into recovery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes

et al. 2021

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“…24 Reproducibility of CMB ratings in the FHS is good to excellent. 25 Presence of CMBs were categorized according to their brain location: any CMB (CMB in any brain region), lobar only, deep only, and mixed location (lobar or deep).…”

Section: Cerebral Microbleedsmentioning

confidence: 99%

Association of Apolipoprotein E ɛ4 Allele with Enlarged Perivascular Spaces

Pinheiro

Demissie

Scruton

et al. 2022

Annals of Neurology

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Objective Enlarged perivascular spaces have emerged as markers of cerebral small vessel disease and are linked to perivascular drainage dysfunction. The apolipoprotein E‐ɛ4 (APOE‐ɛ4) allele is the strongest genetic risk factor for cerebral amyloid angiopathy and Alzheimer's neuropathology, but the underlying mechanisms remain unclear. We studied the relationship between APOE‐ɛ4 and the topography and burden of enlarged perivascular spaces to elucidate underlying mechanisms between APOE‐ɛ4 and adverse clinical outcomes. Methods We included 3,564 Framingham Heart Study participants with available genotypes and magnetic resonance imaging. Enlarged perivascular spaces in the basal ganglia and centrum semiovale were rated using a validated scale. We related APOE‐ɛ4 allele presence to high burden of enlarged perivascular spaces in each region and a mixed score reflecting high burden in both regions using multivariable logistic regression. Exploratory analyses incorporated presence of cerebral microbleeds and assessed effect modification by hypertension. Results Mean age was 60.7 years (SD = 14.6), 1,644 (46.1%) were men, 1,486 (41.8%) were hypertensive, and 836 (23.5%) participants were APOE‐ɛ4 carriers. APOE‐ɛ4 was associated with high burden of enlarged perivascular spaces in the centrum semiovale (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.16, 1.81) and mixed regions (OR = 1.37, 95% CI = 1.11, 1.68). Associations were slightly stronger in hypertensive subjects. Interpretation The APOE‐ɛ4 allele plays a modest role in the burden of enlarged perivascular spaces in the centrum semiovale. Further studies are needed to clarify the underlying small vessel disease type in community‐dwelling individuals with predominant centrum semiovale enlarged perivascular spaces, which may be hypertensive angiopathy in our sample. ANN NEUROL 2022;92:23–31

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Associations of plasma NfL, GFAP, and t-tau with cerebral small vessel disease and incident dementia: longitudinal data of the AGES-Reykjavik Study

van Gennip,

Satizabal,

Tracy

et al. 2023

GeroScience

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We investigated the associations of plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau (t-tau) with markers of cerebral small vessel disease (SVD) and with incident dementia. We also investigated whether associations of NfL, GFAP, and t-tau with incident dementia were explained by SVD. Data are from a random subsample (n = 1069) of the population-based AGES-Reykjavik Study who underwent brain MRI and in whom plasma NfL, GFAP, and t-tau were measured at baseline (76.1 ± 5.4 years/55.9% women/baseline 2002–2006/follow-up until 2015). A composite SVD burden score was calculated using white matter hyperintensity volume (WMHV), subcortical infarcts, cerebral microbleeds, and large perivascular spaces. Dementia was assessed in a 3-step process and adjudicated by specialists. Higher NfL was associated with a higher SVD burden score. Dementia occurred in 225 (21.0%) individuals. The SVD burden score significantly explained part of the association between NfL and incident dementia. WMHV mostly strongly contributed to the explained effect. GFAP was not associated with the SVD burden score, but was associated with WMHV, and WMHV significantly explained part of the association between GFAP and incident dementia. T-tau was associated with WMHV, but not with incident dementia. In conclusion, the marker most strongly related to SVD is plasma NfL, for which the association with WMHV appeared to explain part of its association with incident dementia. This study suggests that plasma NfL may reflect the contribution of co-morbid vascular disease to dementia. However, the magnitude of the explained effect was relatively small, and further research is required to investigate the clinical implications of this finding.

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Relation of plasma β‐amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study

Cited by 21 publications

References 26 publications

Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes

Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes

Association of Apolipoprotein E ɛ4 Allele with Enlarged Perivascular Spaces

Associations of plasma NfL, GFAP, and t-tau with cerebral small vessel disease and incident dementia: longitudinal data of the AGES-Reykjavik Study

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