Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease

Schott, Jonathan M.; Crutch, Sebastian J.; Carrasquillo, Minerva M.; Uphill, James; Shakespeare, Timothy J.; Ryan, Natalie S.; Yong, Keir X. X.; Lehmann, Manja; Ertekin-Taner, Nilüfer; Graff-Radford, Neil; Boeve, Bradley F.; Murray, Melissa E.; Khan, Qurat ul Ain; Petersen, Ronald C.; Dickson, Dennis W.; Knopman, David S.; Rabinovici, Gil D.; Miller, Bruce L.; González, Aida Suárez; Gil-Néciga, E; Snowden, Julie S.; Harris, Jenny; Pickering‐Brown, Stuart; Louwersheimer, Eva; Flier, Wiesje M. van der; Scheltens, Philip; Pijnenburg, Yolande A.L.; Galasko, Douglas; Sarazin, Marie; Dubois, Bruno; Magnin, Éloi; Galimberti, Daniela; Scarpini, Elio; Cappa, Stefano F.; Hodges, John R.; Halliday, Glenda M.; Bartley, Lauren; Carrillo, María C.; Brás, José; Hardy, John; Rossor, Martin N.; Collinge, John; Fox, Nick C.; Mead, Simon

doi:10.1016/j.jalz.2016.01.010

Cited by 100 publications

(87 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, a recent genome-wide association study in posterior cortical atrophy (the “visual variant of AD”) revealed associations with genes involved in neurodevelopment of the visual system and retinal degeneration. 52 …”

Section: Discussionmentioning

confidence: 99%

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Bergeron

Gorno‐Tempini

Rabinovici

et al. 2018

Annals of Neurology

Self Cite

152

111

View full text Add to dashboard Cite

Objective: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebro-spinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. Methods: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models. Results: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid-β positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration–TDP-43 in svPPA (80%), and frontotemporal lobar degeneration–TDP-43/tau in nfvPPA (64%). Interpretation: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-β biomarkers in PPA patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Bergeron

Gorno‐Tempini

Rabinovici

et al. 2018

Annals of Neurology

Self Cite

152

111

View full text Add to dashboard Cite

show abstract

“…Several studies report that APOE e4 frequency is lower in atypical clinical presentations compared to typical AD 23, 45–47 . Our results fit with these findings but extend them to show that a lower APOE e4 frequency is particularly associated with high tau deposition in the cortex but a relative sparing of the ERC.…”

Section: Discussionmentioning

confidence: 99%

[¹⁸F]AV‐1451 clustering of entorhinal and cortical uptake in Alzheimer's disease

Whitwell

Graff‐Radford

Tosakulwong

et al. 2018

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

“…This suggestion is supported by the earlier age at symptom onset reported in individuals with PCA in this study and others, 34,35 by a potential gender bias (with a higher proportion of female patients diagnosed with PCA), 2,13,33,36–38 and by emerging reports identifying putative genetic associations in individuals with PCA. 2,39,40 …”

Section: Discussionmentioning

confidence: 99%

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia

Day¹,

Gordon

Jackson

et al. 2017

Alzheimer Disease &Amp; Associated Disorders

View full text Add to dashboard Cite

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

show abstract

Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease

Cited by 100 publications

References 36 publications

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

[¹⁸F]AV‐1451 clustering of entorhinal and cortical uptake in Alzheimer's disease

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia

Contact Info

Product

Resources

About

Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease

Cited by 100 publications

References 36 publications

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

[18F]AV‐1451 clustering of entorhinal and cortical uptake in Alzheimer's disease

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia

Contact Info

Product

Resources

About

[¹⁸F]AV‐1451 clustering of entorhinal and cortical uptake in Alzheimer's disease