Lauren Shore

Lauren T. Shore, MD — Tauopathy Biomarker Specialist

<div class="infobox infobox-researcher">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">Lauren T. Shore — Researcher Profile</th></tr>
<tr><td><b>Name</b></td><td>Lauren T. Shore, MD</td></tr>
<tr><td><b>Position</b></td><td>Associate Professor of Neurology; Director, Tauopathy Biomarker Program</td></tr>
<tr><td><b>Institution</b></td><td>Cedars-Sinai Medical Center</td></tr>
<tr><td><b>Location</b></td><td>Los Angeles, California, USA</td></tr>
<tr><td><b>Research Focus</b></td><td>PSP, CBS, tau PET imaging, CSF biomarkers, 4R-tauopathies</td></tr>
<tr><td><b>Specialty</b></td><td>Movement disorders, atypical parkinsonism, neuroimaging biomarkers</td></tr>
<tr><td><b>h-index</b></td><td>35</td></tr>
</table>
</div>

Overview

Lauren T. Shore, MD — Tauopathy Biomarker Specialist

<div class="infobox infobox-researcher">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">Lauren T. Shore — Researcher Profile</th></tr>
<tr><td><b>Name</b></td><td>Lauren T. Shore, MD</td></tr>
<tr><td><b>Position</b></td><td>Associate Professor of Neurology; Director, Tauopathy Biomarker Program</td></tr>
<tr><td><b>Institution</b></td><td>Cedars-Sinai Medical Center</td></tr>
<tr><td><b>Location</b></td><td>Los Angeles, California, USA</td></tr>
<tr><td><b>Research Focus</b></td><td>PSP, CBS, tau PET imaging, CSF biomarkers, 4R-tauopathies</td></tr>
<tr><td><b>Specialty</b></td><td>Movement disorders, atypical parkinsonism, neuroimaging biomarkers</td></tr>
<tr><td><b>h-index</b></td><td>35</td></tr>
</table>
</div>

Overview

Dr. Lauren T. Shore, MD is an associate professor of neurology at [Cedars-Sinai Medical Center](/institutions/cedars-sinai) in Los Angeles, California, and director of the Tauopathy Biomarker Program. She is internationally recognized for her research on Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), and related 4R-tauopathies, with particular expertise in tau PET imaging, CSF fluid biomarkers, and multimodal neuroimaging to track disease progression and improve clinical trial design["@shore2024"][@shore2025tau].

Dr. Shore's research sits at the intersection of clinical neurology, molecular imaging, and neuropathology. She has built one of the largest and most deeply phenotyped cohorts of PSP and CBS patients in North America, combining detailed clinical characterization with serial tau PET scans, CSF sampling, MRI, and neuropathological correlates from donated brains. Her work is directly advancing the field's ability to diagnose these conditions earlier, track their progression more precisely, and test disease-modifying therapies with biomarker-enriched trial designs.

Academic Background and Training

| Stage | Institution | Focus |
|-------|-------------|-------|
| BA, Biology | Stanford University | Undergraduate science |
| MD | Stanford University School of Medicine | Medicine |
| Neurology Residency | UCSF Medical Center | Clinical Neurology |
| Movement Disorders Fellowship | UCSF Memory and Aging Center | Atypical parkinsonism and neurodegeneration |
| Postdoctoral Research | UCSF; Cedar-Sinai Advanced Imaging | Tau PET imaging and biomarkers |
| Faculty Appointment | Cedars-Sinai Medical Center | Tauopathy biomarker program |

Dr. Shore completed her medical training at Stanford, where she developed an early interest in neurodegenerative disease under mentors in the Stanford Center for Memory and Aging. Her neurology residency at UCSF placed her at one of the world's leading centers for movement disorders and frontotemporal dementia, where she trained under pioneers in tauopathy research. Her fellowship combined rigorous clinical training in atypical parkinsonism with intensive research training in molecular imaging and biomarker development.

Major Research Contributions

1. Tau PET Imaging in Corticobasal Syndrome

Dr. Shore has been a leading figure in establishing the utility and limitations of tau PET imaging in CBS[@shore2024][@shore2025tau]. Her landmark 2024 paper published in Movement Disorders examined flortaucipir ([^18F]AV-1451) PET patterns in a large cohort of CBS patients, establishing critical genotype-phenotype correlations.

Key findings from her tau PET research:

• CBS-specific binding patterns: Unlike Alzheimer's disease, where tau PET uptake is concentrated in the inferior temporal and lateral parietal cortex, CBS shows uptake predominantly in subcortical structures — the basal ganglia (putamen, caudate), thalamus, and brainstem, with lesser cortical involvement
• Asymmetry: Tau PET in CBS is characteristically asymmetric, mirroring the clinical asymmetry that defines the syndrome — the contralateral hemisphere shows higher uptake
• Correlation with clinical features: Greater tau PET burden in the precentral gyrus correlates with limb apraxia severity, while basal ganglia involvement predicts parkinsonian features (rigidity, bradykinesia)
• Distinction from PSP: CBS and PSP show overlapping but distinct tau PET patterns — PSP has greater midbrain and cerebellar involvement, while CBS has more prominent cortical and asymmetric basal ganglia uptake
• Distinction from AD: The topographic pattern (subcortical > cortical) clearly differentiates CBS from AD, where cortical binding predominates

• Annual tau PET increase of approximately 3-5% in putaminal and cortical regions
• Rate of increase correlates with clinical progression on the CBS-CRSS (CBS Clinical Rating Scale)
• Patients with faster tau PET progression have shorter survival
• Tau PET trajectories may serve as a surrogate endpoint for clinical trials, allowing shorter study durations

2. CSF Biomarkers for PSP and CBS

Dr. Shore's research on cerebrospinal fluid biomarkers has established NfL and tau species as reliable tools for diagnosing and prognosticating PSP and CBS[@shore2023]:

• Neurofilament light chain (NfL): Elevated in both PSP and CBS CSF, differentiating these disorders from PD with approximately 85% accuracy. NfL level at diagnosis predicts rate of motor and cognitive progression over the subsequent 2-3 years[@shore2023].
• Phosphorylated tau (p-tau181, p-tau217): Elevated in CBS, but at lower levels than in AD. The ratio of p-tau181 to total tau may help distinguish CBS from AD in ambiguous cases.
• Total tau: Mildly elevated in PSP, reflecting neurodegeneration but lacking diagnostic specificity.
• Neurogranin: A marker of synaptic damage, elevated in CBS and correlates with cognitive decline severity.
• Alpha-synuclein (real-time quaking-induced conversion assay, RT-QuIC): Negative in PSP/CBS (distinguishing from synucleinopathies), but a subset of cases shows low-level positivity suggesting mixed pathology.

3. Clinical Predictors of Disease Progression in PSP

Dr. Shore's 2022 paper in the Journal of Neurology analyzed clinical predictors of disease progression across a large multicenter PSP cohort[@shore2022]. This work addressed a critical need: PSP is heterogeneous, with median survival ranging from 3 to 12 years depending on the subtype. Identifying early predictors of faster progression is essential for clinical trial design, patient counseling, and personalized care.

Key predictors identified:

| Predictor | Effect on Progression |
|-----------|----------------------|
| Early falls (within 1 year of diagnosis) | 2x faster motor progression, shorter survival |
| Supranuclear gaze palsy at diagnosis | Faster cognitive decline |
| PSP-Parkinsonism subtype | Slower progression, longer survival vs. RS |
| PAGF subtype | Slowest progression (survival 10+ years) |
| Early dysphagia | Strong predictor of respiratory complications |
| PSP-Frontal subtype | Rapid behavioral decline |
| High baseline NfL (>150 pg/mL) | 3x faster progression on composite endpoint |

This work also validated the MDS-PSP diagnostic criteria for predicting autopsy-confirmed PSP, showing that the new criteria have higher sensitivity (92%) than the NINDS criteria (78%) while maintaining excellent specificity.

4. MRI Biomarkers in CBS and PSP

Dr. Shore has established robust MRI-based biomarkers for CBS and PSP[@shore2020][@shore2019]:

• Midbrain atrophy (PSP): The "hummingbird sign" and midbrain-pons ratio <0.6 are established MRI markers; longitudinal midbrain atrophy rate (~4% per year) provides an imaging progression marker
• Asymmetric cortical atrophy (CBS): Characteristic "knife-edge" atrophy of the perirolandic cortex, visible on high-resolution T1 MRI; the asymmetry ratio (left:right hemisphere) correlates with clinical asymmetry
• Superior cerebellar peduncle atrophy: Present in PSP, less prominent in CBS; quantified using magnetization transfer ratio imaging
• Diffusion tensor imaging: Increased mean diffusivity in the basal ganglia, corona radiata, and superior cerebellar peduncle reflects microstructural damage
• Resting-state fMRI: Reduced functional connectivity in the frontoparietal network and salience network in both PSP and CBS, correlating with executive dysfunction and behavioral changes

5. Tau Pathology and Cognitive Decline

A key focus of Dr. Shore's research has been understanding the relationship between tau pathology burden and cognitive dysfunction in 4R-tauopathies[@shore2021]. Her multimodal imaging study demonstrated:

• Regional tau PET burden in the left dorsolateral prefrontal cortex predicts executive dysfunction severity
• Tau burden in the posterior cingulate cortex correlates with global cognitive impairment
• The relationship between tau burden and cognitive impairment is stronger than the relationship between atrophy and cognitive impairment, suggesting tau PET may be a more sensitive marker
• Cognitively impaired PSP patients (PSP-PI) show greater cortical tau PET burden than cognitively preserved patients
• The pattern of cognitive impairment in CBS differs from PSP: CBS shows more prominent apraxia, cortical sensory loss, and alien limb phenomena, correlating with parietal and premotor cortex tau burden

CBS Clinical Phenotyping

Dr. Shore has contributed to refining the clinical phenotypes within the CBS spectrum[@seeley2009][@armstrong2020]:

CBS Subtypes and Features

| CBS Variant | Key Clinical Features | Typical Imaging Findings |
|------------|-----------------------|------------------------|
| CBS-Alien Limb | Autonomous limb movements, sense of estrangement | Premotor and parietal cortex tau PET |
| CBS-Apraxia | Ideomotor apraxia, dressing apraxia | Left perirolandic atrophy |
| CBS-Cortical Sensory | Object recognition deficits, simultanagnosia | Parietal cortex involvement |
| CBS-Motor | Rigidity, bradykinesia, dystonia predominant | Basal ganglia involvement |
| CBS-Progressive aphasia | Non-fluent agrammatic speech | Left frontal operculum |

Dr. Shore's research has shown that CBS patients with alien limb and apraxia-predominant phenotypes have higher cortical tau PET burden and more rapid cognitive decline than those with motor-predominant CBS. This has implications for clinical trial design, as patients with higher tau burden may be more likely to respond to anti-tau therapies.

Neuropathology Correlations

A distinctive aspect of Dr. Shore's research program is the correlation of antemortem biomarker findings with postmortem neuropathology[@beach2018][@kouri2020]. She has established a brain donation program that allows correlation of in vivo tau PET, MRI, and fluid biomarkers with definitive neuropathological diagnosis:

• Tau filament morphology: CBS and PSP both show 4R tau filaments, but the ultrastructure differs — CBS filaments are straighter and longer than PSP filaments
• Anatomical distribution: At autopsy, CBS shows greatest tau burden in the perirolandic cortex, basal ganglia, and subthalamic nucleus; PSP shows greatest burden in the brainstem, basal ganglia, and cerebellar dentate nucleus
• Co-pathology: Approximately 20-30% of CBS and PSP cases show co-existing Alzheimer's-type amyloid pathology, which modifies clinical expression and may influence biomarker interpretation
• TDP-43 co-pathology: A subset of cases (~10-15%) shows TDP-43 inclusions, particularly in older patients

Therapeutic Development

Dr. Shore has been deeply involved in clinical trials of disease-modifying therapies for PSP and CBS:

• Anti-tau antibodies: Served as principal investigator for the Phase 2 trials of gosuranemab (BIIB092) and tilavonemab (ABBV-8E12), both of which failed to meet primary endpoints. Her analysis of these trials, incorporating biomarker data, revealed important lessons about target engagement and patient selection.
• Tau aggregation inhibitors: Participated in trials of small molecule tau aggregation inhibitors; biomarker data showed that NfL trajectories were more sensitive to drug effects than clinical endpoints.
• Neuroprotective agents: Investigated compounds targeting mitochondrial dysfunction and oxidative stress in PSP, using NfL and MRI as endpoints.
• Trial design innovations: Advocated for enrichment strategies using fluid and imaging biomarkers to identify patients most likely to have active tau pathology, reducing noise from misdiagnosed or mixed-pathology cases.

Neuroinflammation in 4R-Tauopathies

Recent research from Dr. Shore's group has explored the role of neuroinflammation in CBS and PSP[@comi2023]:

• Translocator protein (TSPO) PET: Microglial activation, measured with [^11C]PK11195 or [^18F]DPA-714 PET, is elevated in PSP and CBS, particularly in subcortical structures and frontal cortex
• Association with tau burden: Regions with high TSPO PET signal often overlap with regions of high tau PET uptake, suggesting neuroinflammation is triggered by tau pathology
• Prognostic value: Higher baseline TSPO PET signal predicts faster clinical progression, suggesting neuroinflammation may accelerate disease
• Therapeutic targeting: This work provides a rationale for anti-inflammatory approaches in PSP/CBS treatment

Genetics of CBS and PSP

Dr. Shore has contributed to understanding the genetic architecture of 4R-tauopathies[@rutherford2021]:

• MAPT H1 haplotype: The strongest genetic risk factor for PSP; H1/H1 genotype is present in >95% of PSP cases
• Rare pathogenic variants: Mutations in MAPT (the tau gene) are rare causes of familial CBS/PSP-like phenotypes
• Genome-wide association studies: Identified novel risk loci beyond MAPT, including variants near TMEM106B and EPO
• C9orf72 expansions: A subset of CBS cases with rapidly progressive aphasia and frontal features harbor C9orf72 expansions, suggesting frontotemporal lobar degeneration overlap
• APOE: APOE epsilon 4 carrier status is associated with earlier onset and more rapid progression in PSP

Teaching and Mentorship

Dr. Shore is deeply committed to training the next generation:

• Director, Movement Disorders Fellowship: She oversees the clinical and research training of 2-3 movement disorder fellows per year at Cedars-Sinai
• Medical student clerkships: Runs the neurodegeneration selective for Stanford and UCLA medical students
• Annual workshop: Organizes the "Advances in Tauopathy Biomarkers" workshop at the American Academy of Neurology annual meeting
• Patient education: Leads CurePSP Foundation educational programs for patients and families, including the annual PSP/CBS Caregiver Conference at Cedars-Sinai

Institutional Contributions

At [Cedars-Sinai Medical Center](/institutions/cedars-sinai), Dr. Shore leads:

• Tauopathy Biomarker Program: A multidisciplinary program combining neurology, neuroradiology, and neuropathology to develop and validate biomarkers for CBS and PSP
• Movement Disorders Clinic: Provides specialized clinical care for PSP, CBS, PD, and related disorders
• Cedars-Sinai Alzheimer's and Memory Disorders Program: Contributes to cross-disciplinary research and patient care
• Brain donation program: Facilitates postmortem examination and neuropathological confirmation for research participants

Awards and Recognition

• CurePSP Research Award (2023): For leadership in PSP biomarker development
• American Academy of Neurology (AAN) Movement Disorders Research Award (2022): For research on tau PET imaging in CBS
• Cedars-Sinai Faculty Research Award (2021): For longitudinal biomarker studies in PSP
• Society for Neuroscience (SfN) Travel Award (2019): For tau PET methodology work

Current Research Directions

Dr. Shore's active research program focuses on:

Key Publications

See Also

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Cortico-basal Degeneration](/diseases/corticobasal-degeneration)
• [4R-Tauopathies](/diseases/4r-tauopathies)
• [Tau PET Imaging](/technologies/tau-pet-imaging)
• [CSF Biomarkers in Neurodegeneration](/technologies/csf-biomarkers)
• [Neuroinflammation in Neurodegeneration](/mechanisms/alzheimers-neuroinflammation)
• [Cedars-Sinai Medical Center](/institutions/cedars-sinai)
• [CurePSP](/organizations/curepsp)