Anna Steward

Ludwig-Maximilians-University of Munich | LMU · Institute for Stroke and Dementia Research (ISD)

Background Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4‐repeat (4R) tauopathies and its role in accelerating disease progression. Objective We tested whether microglial activation (1) progresses in similar spatial patterns as the...

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and g...

In Alzheimer’s disease, amyloid-beta (Aβ) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. Aβ induces aberrant synaptic activity, manifesting in increases in the presynaptic growth-associated protein 43 (GAP-43), which is closely involved in synaptic activity and plasticity...

Background Recent post‐mortem studies suggest that cerebrovascular disease contributes to Alzheimer’s disease (AD) pathophysiology and clinical progression. In particular, cerebral amyloid angiopathy is highly common in AD and has been linked to faster cognitive decline. Yet, in‐vivo evidence on the contribution of cerebrovascular disease to pathob...

Background In Alzheimer’s disease (AD), Amyloid‐beta deposition (Ab) is associated with tau spreading from epicenters to connected regions. Yet, Ab and tau accumulate in strikingly different patterns, and it is unclear how Abdrives tau spreading. We envision two mechanisms, i.e. i) that cortical Ab exerts remote effects and “pulls” tau out of conne...

Background Targeting amyloid (Aß) may show highest clinical efficacy when preventing downstream tau spreading and subsequent neurodegeneration. Thus, it’s critical to establish Aß‐PET thresholds at which tau spreading is triggered, which may depend on ApoE4, i.e. a key genetic risk factor for Aß, tau and cognitive decline. Yet, ApoE4’s impact on Aß...

Background Animal and in vitro studies of Alzheimer’s disease (AD) found that tau spreads trans‐synaptically in an activity‐dependent manner, suggesting that synapses are key routes for tau spread. Importantly, amyloid‐beta (Ab) induces synaptic remodeling and aberrant synaptic activity, which may accelerate trans‐synaptic tau spread. In AD patient...

Background State‐of‐the‐art preprocessing of MRI and PET data is crucial for Alzheimer’s disease (AD) neuroimaging research. Therefore, standardization and harmonization of neuroimaging preprocessing across sites is key to generate comparable and sharable datasets and to reduce potential bias introduced by different preprocessing strategies. Furthe...

Background State‐of‐the‐art preprocessing of MRI and PET data is crucial for Alzheimer’s disease (AD) neuroimaging research. Therefore, standardization and harmonization of neuroimaging preprocessing across sites is key to generate comparable and sharable datasets and to reduce potential bias introduced by different preprocessing strategies. Furthe...

Background Recent post‐mortem studies suggest that cerebrovascular disease contributes to Alzheimer’s disease (AD) pathophysiology and clinical progression. In particular, cerebral amyloid angiopathy is highly common in AD and has been linked to faster cognitive decline. Yet, in‐vivo evidence on the contribution of cerebrovascular disease to pathob...

Background Animal and in vitro studies of Alzheimer’s disease (AD) found that tau spreads trans‐synaptically in an activity‐dependent manner, suggesting that synapses are key routes for tau spread. Importantly, amyloid‐beta (Ab) induces synaptic remodeling and aberrant synaptic activity, which may accelerate trans‐synaptic tau spread. In AD patient...

Background Targeting amyloid (Aß) may show highest clinical efficacy when preventing downstream tau spreading and subsequent neurodegeneration. Thus, it’s critical to establish Aß‐PET thresholds at which tau spreading is triggered, which may depend on ApoE4, i.e. a key genetic risk factor for Aß, tau and cognitive decline. Yet, ApoE4’s impact on Aß...

Background In Alzheimer’s disease (AD), Amyloid‐beta deposition (Ab) is associated with tau spreading from epicenters to connected regions. Yet, Ab and tau accumulate in strikingly different patterns, and it is unclear how Abdrives tau spreading. We envision two mechanisms, i.e. i) that cortical Ab exerts remote effects and “pulls” tau out of conne...

Importance For the Alzheimer disease (AD) therapies to effectively attenuate clinical progression, it may be critical to intervene before the onset of amyloid-associated tau spreading, which drives neurodegeneration and cognitive decline. Time points at which amyloid-associated tau spreading accelerates may depend on individual risk factors, such a...

Microglial activation occurs early in Alzheimer's disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Here, we used CSF sTREM2 to investigate disease stage-dependent drivers of microglial activation and to determine downstream consequences on AD progression. We included 402 patients wit...

Alzheimer’s disease (AD) is characterized by Aβ and tau accumulation, microglial activation, metabolic brain changes, neurodegeneration, and cognitive decline. Studies found both detrimental and protective effects of microglial activation on AD progression, hence neuroinflammation may be a double‐edged sword in AD, which is critical for clinical tr...

In Alzheimer’s disease (AD), the functional connectome plays a key role in the trans‐neuronal spreading of tau pathology, a key driver of cognitive decline. The functional connectome is comprised of segregated, but communicating networks which lose segregation with age, resulting in an overall more diffuse connectome. Prior neuroimaging studies hav...

In Alzheimer’s disease (AD), younger symptom onset is associated accelerated cognitive decline and tau spreading, yet the drivers of faster disease manifestation in patients with earlier symptom onset are unknown. Earlier symptom onset is associated with stronger tau pathology in fronto‐parietal regions which typically harbor globally connected hub...

In Alzheimer’s disease (AD), younger symptom onset is associated accelerated cognitive decline and tau spreading, yet the drivers of faster disease manifestation in patients with earlier symptom onset are unknown. Earlier symptom onset is associated with stronger tau pathology in fronto‐parietal regions which typically harbor globally connected hub...

4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hyp...

In Alzheimer’s disease (AD), the functional connectome plays a key role in the trans‐neuronal spreading of tau pathology, a key driver of cognitive decline. The functional connectome is comprised of segregated, but communicating networks which lose segregation with age, resulting in an overall more diffuse connectome. Prior neuroimaging studies hav...

4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hyp...

Introduction: Lower network segregation is associated with accelerated cognitive decline in Alzheimer's disease (AD), yet it is unclear whether less segregated brain networks facilitate connectivity-mediated tau spreading. Methods: We combined resting state functional magnetic resonance imaging (fMRI) with longitudinal tau positron emission tomo...

Background Tau-PET is a prognostic marker for cognitive decline in Alzheimer’s disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints...

Although memory is known to play a key role in creativity, previous studies have not isolated the critical component processes and networks. We asked participants to generate links between words that ranged from strongly related to completely unrelated in long-term memory, delineating the neurocognitive processes that underpin more unusual versus s...

Background Microglial activation occurs early in Alzheimer’s disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Therefore, it is critical to investigate at which AD stages microglial activation could be protective or detrimental to evaluate microglia as a treatment target. To address t...

In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/Bio...

While memory is known to play a key role in creativity, previous studies have not isolated the critical component processes and networks. We asked participants to generate links between words that ranged from strongly related to completely unrelated in long-term memory, delineating the neurocognitive processes that underpin more unique versus stere...