Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

Montoliu‐Gaya, Laia; Strydom, André; Blennow, Kaj; Zetterberg, Henrik; Ashton, Nicholas J.

doi:10.3390/jcm10163639

Cited by 19 publications

(23 citation statements)

References 132 publications

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“…Pretangle Tau, thought to be the toxic form of tau, has now been detected in MCI and AD and has been found to be one of the earliest tau lesions that correlates with cognitive status (Mufson et al, 2014). Synapse loss (Bastin et al, 2020;Buchanan et al, 2020;Mecca et al, 2020;Pereira et al, 2021), changes in hormone levels (Cheng et al, 2021), changes in blood biomarker levels (Guzman-Martinez et al, 2019;Montoliu-Gaya et al, 2021), electroencephalogram (EEG) readings (Hulbert and Adeli, 2013;Lin et al, 2021), retinal assays (Ashok et al, 2020;Mirzaei et al, 2020), and changes in specific protein levels (Buchanan et al, 2020;Colom-Cadena et al, 2020) are some of the myriad assays being developed to try to detect AD earlier and predict when and if the change from mild cognitive impairment (MCI) to AD will occur (Zhang T. et al, 2021). All of these new developments are focused toward enabling earlier therapeutic intervention when chances for success would be greatest.…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

et al. 2022

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Improvements have been made in the diagnosis of Alzheimer’s disease (AD), manifesting mostly in the development of in vivo imaging methods that allow for the detection of pathological changes in AD by magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques–species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression. Here we report evidence further supporting the role of AβOs as pathological instigators of AD and introduce promising anti-AβO diagnostic probes capable of distinguishing the 5xFAD mouse model from wild type mice by PET and MRI. In a developmental study, Aβ oligomers in 5xFAD mice were found to appear at 3 months of age, just prior to the onset of memory dysfunction, and spread as memory worsened. The increase of AβOs is prominent in the subiculum and correlates with concomitant development of reactive astrocytosis. The impact of these AβOs on memory is in harmony with findings that intraventricular injection of synthetic AβOs into wild type mice induced hippocampal dependent memory dysfunction within 24 h. Compelling support for the conclusion that endogenous AβOs cause memory loss was found in experiments showing that intranasal inoculation of AβO-selective antibodies into 5xFAD mice completely restored memory function, measured 30–40 days post-inoculation. These antibodies, which were modified to give MRI and PET imaging probes, were able to distinguish 5xFAD mice from wild type littermates. These results provide strong support for the role of AβOs in instigating memory loss and salient AD neuropathology, and they demonstrate that AβO selective antibodies have potential both for therapeutics and for diagnostics.

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Section: Discussionmentioning

confidence: 99%

The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

et al. 2022

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“…Pre-tangle Tau, thought to be the toxic form of tau, has now been detected in MCI and AD and has been found to be one of the earliest tau lesions that correlates with cognitive status (Mufson et al, 2014). Synapse loss (Bastin et al, 2020;Buchanan et al, 2020;Camporesi et al, 2020;Mecca et al, 2020;Pereira et al, 2021), changes in hormone levels (Cheng et al, 2021), changes in blood biomarker levels (Guzman-Martinez et al, 2019;Montoliu-Gaya et al, 2021), electroencephalogram (EEG) readings (Hulbert and Adeli, 2013;Siwek et al, 2015;Lin et al, 2021), retinal assays (Ashok et al, 2020;Mirzaei et al, 2020), and changes in specific protein levels P a g e 16 | 34 (Buchanan et al, 2020;Colom-Cadena et al, 2020) are some of the myriad assays being developed to try to detect AD earlier and predict when and if the change from mild cognitive impairment (MCI) to AD will occur (Zhang et al, 2021b). All of these new developments are focused towards enabling earlier therapeutic intervention when chances for success would be greatest.…”

Section: Discussionmentioning

confidence: 99%

The therapeutic and diagnostic potential of amyloid β oligomers (AβOs) selective antibodies to treat Alzheimer’s disease

Viola

Bicca

Bebenek

et al. 2021

Preprint

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Improvements have been made in the diagnosis of Alzheimer's disease (AD), manifesting mostly in the development of in vivo imaging methods that allow for the detection of pathological changes in AD by MRI and PET scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques- species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression. Here we report evidence further supporting the role of AβOs as pathological instigators of AD and introduce a promising anti-AβO diagnostic probe capable of distinguishing the 5xFAD mouse model from wild type mice by PET and MRI. In a developmental study, Aβ oligomers in 5xFAD mice were found to appear at 3 months of age, just prior to the onset of memory dysfunction, and spread as memory worsened. The increase is prominent in the subiculum and correlates with concomitant development of reactive astrocytosis. The impact of these AβOs on memory is in harmony with findings that intraventricular injection of synthetic AβOs into wild type mice induced hippocampal dependent memory dysfunction within 24 hours. Compelling support for the conclusion that endogenous AβOs cause memory loss was found in experiments showing that intranasal inoculation of AβO-selective antibodies into 5xFAD mice completely restored memory function, measured 30 days post-inoculation. These antibodies, which were modified to give MRI and PET imaging probes, were able to distinguish 5xFAD mice from wild type littermates. These results provide strong support for the role of AβOs in instigating memory loss and salient AD neuropathology, and they demonstrate that AβO selective antibodies have potential both for therapeutics and for diagnostics.

show abstract

“…These biomarkers have been investigated in longitudinal cohorts of sporadic and familial AD, and in recent years, also in DS. 7 As it is the case in AD, plasma Aβ42/Aβ40 and total-tau, at least with currently available methods, have shown low diagnostic performance. Additionally, plasma pTau181 has been proven to differentiate people with DS with and without dementia with high accuracy, but no better than NfL.…”

mentioning

confidence: 99%

Commentary on Oeckl et al., “Serum Beta‐Synuclein Is Higher in Down Syndrome and Precedes Rise of pTau181”

Head

Zetterberg

2022

Annals of Neurology

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Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

Cited by 19 publications

References 132 publications

The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

The therapeutic and diagnostic potential of amyloid β oligomers (AβOs) selective antibodies to treat Alzheimer’s disease

Commentary on Oeckl et al., “Serum Beta‐Synuclein Is Higher in Down Syndrome and Precedes Rise of pTau181”

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