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Your search keyword '"The Dominantly Inherited Alzheimer Network"' showing total 6 results
Start Over Author "The Dominantly Inherited Alzheimer Network" Journal research outputs 2022 to 2026
6 results on '"The Dominantly Inherited Alzheimer Network"'

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Author

Chatterjee, Pratishtha, Vermunt, Lisa, Gordon, Brian A., Pedrini, Steve, Boonkamp, Lynn, Armstrong, Nicola J., Xiong, Chengjie, Singh, Abhay K., Li, Yan, Sohrabi, Hamid R., Taddei, Kevin, Molloy, Mark, Benzinger, Tammie L. S., Morris, John C., Karch, Celeste, Berman, Sarah, Chhatwal, Jasmeer, Cruchaga, Carlos, Graff-Radford, Neill R., Day, Gregory S., Farlow, Martin, Fox, Nick, Goate, Alison, Hassenstab, Jason, Lee, Jae-Hong, Levin, Johannes, McDade, Eric, Mori, Hiroshi, Perrin, Richard, Sanchez-Valle, Raquel, Schofield, Peter R., Levey, Allan, Jucker, Mathias, Masters, Colin L., Fagan, Anne M., Bateman, Randall J., Martins, Ralph N., Teunissen, Charlotte, Dominantly Inherited Alzheimer Network, Chatterjee, Pratishtha, Vermunt, Lisa, Gordon, Brian A., Pedrini, Steve, Boonkamp, Lynn, Armstrong, Nicola J., Xiong, Chengjie, Singh, Abhay K., Li, Yan, Sohrabi, Hamid R., Taddei, Kevin, Molloy, Mark, Benzinger, Tammie L. S., Morris, John C., Karch, Celeste, Berman, Sarah, Chhatwal, Jasmeer, Cruchaga, Carlos, Graff-Radford, Neill R., Day, Gregory S., Farlow, Martin, Fox, Nick, Goate, Alison, Hassenstab, Jason, Lee, Jae-Hong, Levin, Johannes, McDade, Eric, Mori, Hiroshi, Perrin, Richard, Sanchez-Valle, Raquel, Schofield, Peter R., Levey, Allan, Jucker, Mathias, Masters, Colin L., Fagan, Anne M., Bateman, Randall J., Martins, Ralph N., Teunissen, Charlotte, and Dominantly Inherited Alzheimer Network

Abstract

Background: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. Methods: We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Results: Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (A ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished A -positive from A -negative ADAD participants and showed a stronger relationship with A load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. Conclusion: Our findings support a role for plasma GFAP as a clinical biomarker of A -related astrocyte reactivity that is associated with cognitive decline and neurodegeneration. Highlights: Plasma glial fibrillary acidic protein (GFAP) elevations appear a decade before expected symptom onset in autosomal dominant Alzheimer's disease (ADAD). Plasma GFAP was associated to amyloid positivity in asymptomatic ADAD. Plasma GFAP increased with clinical severity and predicted disease progression. Plasma and serum GFAP carried similar information in ADAD, while cerebrospinal fluid GFAP did not.

Published
2023

2. Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer's disease

Author

Schultz, Stephanie A., Shirzadi, Zahra, Schultz, Aaron P., Liu, Lei, Fitzpatrick, Colleen D., McDade, Eric, Barthelemy, Nicolas R., Renton, Alan, Esposito, Bianca, Joseph-Mathurin, Nelly, Cruchaga, Carlos, Chen, Charles D., Goate, Alison, Allegri, Ricardo F., Benzinger, Tammie L. S., Berman, Sarah, Chui, Helena C., Fagan, Anne M., Farlow, Martin R., Fox, Nick C., Gordon, Brian A., Day, Gregory S., Graff-Radford, Neill R., Hassenstab, Jason J., Hanseeuw, Bernard J., Hofmann, Anna, Jack Jr, Clifford R., Jucker, Mathias, Karch, Celeste M., Koeppe, Robert A., Lee, Jae-Hong, Levey, Allan I., Levin, Johannes, Martins, Ralph, Mori, Hiroshi, Morris, John C., Noble, James, Perrin, Richard J., Rosa-Neto, Pedro, Salloway, Stephen P., Sanchez-Valle, Raquel, Schofield, Peter R., Xiong, Chengjie, Johnson, Keith A., Bateman, Randall J., Sperling, Reisa A., Chhatwal, Jasmeer P., Dominantly Inherited Alzheimer Network Investigators, Schultz, Stephanie A., Shirzadi, Zahra, Schultz, Aaron P., Liu, Lei, Fitzpatrick, Colleen D., McDade, Eric, Barthelemy, Nicolas R., Renton, Alan, Esposito, Bianca, Joseph-Mathurin, Nelly, Cruchaga, Carlos, Chen, Charles D., Goate, Alison, Allegri, Ricardo F., Benzinger, Tammie L. S., Berman, Sarah, Chui, Helena C., Fagan, Anne M., Farlow, Martin R., Fox, Nick C., Gordon, Brian A., Day, Gregory S., Graff-Radford, Neill R., Hassenstab, Jason J., Hanseeuw, Bernard J., Hofmann, Anna, Jack Jr, Clifford R., Jucker, Mathias, Karch, Celeste M., Koeppe, Robert A., Lee, Jae-Hong, Levey, Allan I., Levin, Johannes, Martins, Ralph, Mori, Hiroshi, Morris, John C., Noble, James, Perrin, Richard J., Rosa-Neto, Pedro, Salloway, Stephen P., Sanchez-Valle, Raquel, Schofield, Peter R., Xiong, Chengjie, Johnson, Keith A., Bateman, Randall J., Sperling, Reisa A., Chhatwal, Jasmeer P., and Dominantly Inherited Alzheimer Network Investigators

Published
2023

3. Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease

Author

Ali, Muhammad, Archer, Derek B., Gorijala, Priyanka, Western, Daniel, Timsina, Jigyasha, Fernández, Maria V., Wang, Ting Chen, Satizabal, Claudia L., Yang, Qiong, Beiser, Alexa S., Wang, Ruiqi, Chen, Gengsheng, Gordon, Brian, Benzinger, Tammie L.S., Xiong, Chengjie, Morris, John C., Bateman, Randall J., Karch, Celeste M., McDade, Eric, Goate, Alison, Seshadri, Sudha, Mayeux, Richard P., Sperling, Reisa A., Buckley, Rachel F., Johnson, Keith A., Won, Hong-Hee, Jung, Sang-Hyuk, Kim, Hang-Rai, Seo, Sang W., Kim, Hee J., Mormino, Elizabeth, Laws, Simon M., Fan, Kang-Hsien, Kamboh, M. Ilyas, Vemuri, Prashanthi, Ramanan, Vijay K., Yang, Hyun-Sik, Wenzel, Allen, Rajula, Hema S. R., Mishra, Aniket, Dufouil, Carole, Debette, Stephanie, Lopez, Oscar L., DeKosky, Steven T., Tao, Feifei, Nagle, Michael W., Hohman, Timothy J., Sung, Yun J., Dumitrescu, Logan, Cruchaga, Carlos, Knight Alzheimer Disease Research Center (Knight ADRC), the Dominantly Inherited Alzheimer Network (DIAN), Alzheimer's Disease Neuroimaging Initiative (ADNI), ADNI-DOD, A4 Study Team, the Australian Imaging Biomarkers, Lifestyle (AIBL) Study, Ali, Muhammad, Archer, Derek B., Gorijala, Priyanka, Western, Daniel, Timsina, Jigyasha, Fernández, Maria V., Wang, Ting Chen, Satizabal, Claudia L., Yang, Qiong, Beiser, Alexa S., Wang, Ruiqi, Chen, Gengsheng, Gordon, Brian, Benzinger, Tammie L.S., Xiong, Chengjie, Morris, John C., Bateman, Randall J., Karch, Celeste M., McDade, Eric, Goate, Alison, Seshadri, Sudha, Mayeux, Richard P., Sperling, Reisa A., Buckley, Rachel F., Johnson, Keith A., Won, Hong-Hee, Jung, Sang-Hyuk, Kim, Hang-Rai, Seo, Sang W., Kim, Hee J., Mormino, Elizabeth, Laws, Simon M., Fan, Kang-Hsien, Kamboh, M. Ilyas, Vemuri, Prashanthi, Ramanan, Vijay K., Yang, Hyun-Sik, Wenzel, Allen, Rajula, Hema S. R., Mishra, Aniket, Dufouil, Carole, Debette, Stephanie, Lopez, Oscar L., DeKosky, Steven T., Tao, Feifei, Nagle, Michael W., Hohman, Timothy J., Sung, Yun J., Dumitrescu, Logan, Cruchaga, Carlos, Knight Alzheimer Disease Research Center (Knight ADRC), the Dominantly Inherited Alzheimer Network (DIAN), Alzheimer's Disease Neuroimaging Initiative (ADNI), ADNI-DOD, A4 Study Team, and the Australian Imaging Biomarkers, Lifestyle (AIBL) Study

Abstract

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (AB) deposits in the brain and to study Alzheimer’s disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE 4; rs429358; = 0.35, SE = 0.01, P = 6.2 × 10–311, MAF = 0.19), driven by APOE 4, and five additional novel associations (APOE 2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE 4. APOE 4 and 2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; = 0.07, SE = 0.01, P = 9.2 × 10–09, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; = 0.1, SE = 0.02, P = 2.4 × 10–10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; = 0.16, SE = 0.03, P = 1.1 × 10–09, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, = 0.79, SE = 0.14, P = 1.4 × 10–08, MAF = 0.006, sex-interaction P = 9.8 × 10–07) and chr11p.15.2 (rs192346166, = 0.94, SE = 0.17, P = 3.7 × 10–08, MAF = 0.004, sex-interaction P = 1.3 × 10–03). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.

Published
2023

4. Positron emission tomography and magnetic resonance imaging methods and datasets within the dominantly inherited Alzheimer network (DIAN)

Author

McKay, Nicole S., Gordon, Brian A., Hornbeck, Russ C., Dincer, Aylin, Flores, Shaney, Keefe, Sarah J., Joseph-Mathurin, Nelly, Jack, Clifford R., Koeppe, Robert, Millar, Peter R., Ances, Beau M., Chen, Charles D., Daniels, Alisha, Hobbs, Diana A., Jackson, Kelley, Koudelis, Deborah, Massoumzadeh, Parinaz, McCullough, Austin, Nickels, Michael L., Rahmani, Farzaneh, Swisher, Laura, Wang, Qing, Allegri, Ricardo F., Berman, Sarah B., Brickman, Adam M., Brooks, William S., Cash, David M., Chhatwal, Jasmeer P., Day, Gregory S., Farlow, Martin R., la Fougère, Christian, Fox, Nick C., Fulham, Michael, Ghetti, Bernardino, Graff-Radford, Neill, Ikeuchi, Takeshi, Klunk, William, Lee, Jae-Hong, Levin, Johannes, Martins, Ralph, Masters, Colin L., McConathy, Jonathan, Mori, Hiroshi, Noble, James M., Reischl, Gerald, Rowe, Christopher, Salloway, Stephen, Sanchez-Valle, Raquel, Schofield, Peter R., Shimada, Hiroyuki, Shoji, Mikio, Su, Yi, Suzuki, Kazushi, Vöglein, Jonathan, Yakushev, Igor, Cruchaga, Carlos, Hassenstab, Jason, Karch, Celeste, McDade, Eric, Perrin, Richard J., Xiong, Chengjie, Morris, John C., Bateman, Randall J., Benzinger, Tammie L. S., Dominantly Inherited Alzheimer Network, McKay, Nicole S., Gordon, Brian A., Hornbeck, Russ C., Dincer, Aylin, Flores, Shaney, Keefe, Sarah J., Joseph-Mathurin, Nelly, Jack, Clifford R., Koeppe, Robert, Millar, Peter R., Ances, Beau M., Chen, Charles D., Daniels, Alisha, Hobbs, Diana A., Jackson, Kelley, Koudelis, Deborah, Massoumzadeh, Parinaz, McCullough, Austin, Nickels, Michael L., Rahmani, Farzaneh, Swisher, Laura, Wang, Qing, Allegri, Ricardo F., Berman, Sarah B., Brickman, Adam M., Brooks, William S., Cash, David M., Chhatwal, Jasmeer P., Day, Gregory S., Farlow, Martin R., la Fougère, Christian, Fox, Nick C., Fulham, Michael, Ghetti, Bernardino, Graff-Radford, Neill, Ikeuchi, Takeshi, Klunk, William, Lee, Jae-Hong, Levin, Johannes, Martins, Ralph, Masters, Colin L., McConathy, Jonathan, Mori, Hiroshi, Noble, James M., Reischl, Gerald, Rowe, Christopher, Salloway, Stephen, Sanchez-Valle, Raquel, Schofield, Peter R., Shimada, Hiroyuki, Shoji, Mikio, Su, Yi, Suzuki, Kazushi, Vöglein, Jonathan, Yakushev, Igor, Cruchaga, Carlos, Hassenstab, Jason, Karch, Celeste, McDade, Eric, Perrin, Richard J., Xiong, Chengjie, Morris, John C., Bateman, Randall J., Benzinger, Tammie L. S., and Dominantly Inherited Alzheimer Network

Abstract

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case–control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual’s point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of ‘sporadic’ AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers.

Published
2023

5. Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease

Author

Johnson, Erik C. B., Bian, Shijia, Haque, Rafi U., Carter, E. Kathleen, Watson, Caroline M., Gordon, Brian A., Ping, Lingyan, Duong, Duc M., Epstein, Michael P., McDade, Eric, Barthélemy, Nicolas R., Karch, Celeste M., Xiong, Chengjie, Cruchaga, Carlos, Perrin, Richard J., Wingo, Aliza P., Wingo, Thomas S., Chhatwal, Jasmeer P., Day, Gregory S., Noble, James M., Berman, Sarah B., Martins, Ralph, Graff-Radford, Neill R., Schofield, Peter R., Ikeuchi, Takeshi, Mori, Hiroshi, Levin, Johannes, Farlow, Martin, Lah, James J., Haass, Christian, Jucker, Mathias, Morris, John C., Benzinger, Tammie L. S., Roberts, Blaine R., Bateman, Randall J., Fagan, Anne M., Seyfried, Nicholas T., Levey, Allan I., Dominantly Inherited Alzheimer Network, Johnson, Erik C. B., Bian, Shijia, Haque, Rafi U., Carter, E. Kathleen, Watson, Caroline M., Gordon, Brian A., Ping, Lingyan, Duong, Duc M., Epstein, Michael P., McDade, Eric, Barthélemy, Nicolas R., Karch, Celeste M., Xiong, Chengjie, Cruchaga, Carlos, Perrin, Richard J., Wingo, Aliza P., Wingo, Thomas S., Chhatwal, Jasmeer P., Day, Gregory S., Noble, James M., Berman, Sarah B., Martins, Ralph, Graff-Radford, Neill R., Schofield, Peter R., Ikeuchi, Takeshi, Mori, Hiroshi, Levin, Johannes, Farlow, Martin, Lah, James J., Haass, Christian, Jucker, Mathias, Morris, John C., Benzinger, Tammie L. S., Roberts, Blaine R., Bateman, Randall J., Fagan, Anne M., Seyfried, Nicholas T., Levey, Allan I., and Dominantly Inherited Alzheimer Network

Abstract

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid- (A ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of A plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with A plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than A and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with A and tau.

Published
2023

6. Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease

Author

Vöglein, Jonathan, Franzmeier, Nicolai, Morris, John C., Dieterich, Marianne, McDade, Eric, Simons, Mikael, Preische, Oliver, Hofmann, Anna, Hassenstab, Jason, Benzinger, Tammie L., Fagan, Anne, Noble, James M., Berman, Sarah B., Graff-Radford, Neill R., Ghetti, Bernardino, Farlow, Martin R., Chhatwal, Jasmeer P., Salloway, Stephen, Xiong, Chengjie, Karch, Celeste M., Cairns, Nigel, Perrin, Richard J., Day, Gregory, Martins, Ralph, Sanchez-Valle, Raquel, Mori, Hiroshi, Shimada, Hiroyuki, Ikeuchi, Takeshi, Suzuki, Kazushi, Schofield, Peter R., Masters, Colin L., Goate, Alison, Buckles, Virginia, Fox, Nick C., Chrem, Patricio, Allegri, Ricardo, Ringman, John M., Yakushev, Igor, Laske, Christoph, Jucker, Mathias, Höglinger, Günter, Bateman, Randall L., Danek, Adrian, Levin, Johannes, Dominantly Inherited Alzheimer Network, Vöglein, Jonathan, Franzmeier, Nicolai, Morris, John C., Dieterich, Marianne, McDade, Eric, Simons, Mikael, Preische, Oliver, Hofmann, Anna, Hassenstab, Jason, Benzinger, Tammie L., Fagan, Anne, Noble, James M., Berman, Sarah B., Graff-Radford, Neill R., Ghetti, Bernardino, Farlow, Martin R., Chhatwal, Jasmeer P., Salloway, Stephen, Xiong, Chengjie, Karch, Celeste M., Cairns, Nigel, Perrin, Richard J., Day, Gregory, Martins, Ralph, Sanchez-Valle, Raquel, Mori, Hiroshi, Shimada, Hiroyuki, Ikeuchi, Takeshi, Suzuki, Kazushi, Schofield, Peter R., Masters, Colin L., Goate, Alison, Buckles, Virginia, Fox, Nick C., Chrem, Patricio, Allegri, Ricardo, Ringman, John M., Yakushev, Igor, Laske, Christoph, Jucker, Mathias, Höglinger, Günter, Bateman, Randall L., Danek, Adrian, Levin, Johannes, and Dominantly Inherited Alzheimer Network

Abstract

Introduction: As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD. Methods: Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers. Results: AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1 %. Cross-sectionally, mutation carriers with AD neurological examination findings showed a more than two-fold faster cognitive decline and had greater parieto-temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time. Discussion: ADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs.

Published
2023

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