Tags

Type your tag names separated by a space and hit enter

Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study.
Lancet Neurol. 2012 Dec; 11(12):1057-65.LN

Abstract

BACKGROUND

Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimer's disease. By assessing the accumulation of Aβ in people at risk of genetic forms of Alzheimer's disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease.

METHODS

Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer's disease Colombian kindred aged 18-60 years were recruited from the Alzheimer's Prevention Initiative's registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimer's Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions.was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition.

FINDINGS

We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3-33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. (18)F florbetapir binding rose steeply over the next 9·4 years and plateaued at a mean age of 37·6 years (95% CI 35·3-40·2), about 6 and 11 years before the expected respective median ages at mild cognitive impairment and dementia onset. Prominent florbetapir binding was seen in the anterior and posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as well as in the basal ganglia. Binding in the basal ganglia was not seen earlier or more prominently than in other regions.

INTERPRETATION

These findings contribute to the understanding of preclinical familial Alzheimer's disease and help set the stage for assessment of amyloid-modifying treatments in the prevention of familial Alzheimer's disease.

FUNDING

Avid Radiopharmaceuticals, Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona.

Authors+Show Affiliations

Banner Alzheimer's Institute, Phoenix, AZ, USA. adam.fleisher@bannerhealth.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23137949

Citation

Fleisher, Adam S., et al. "Florbetapir PET Analysis of Amyloid-β Deposition in the Presenilin 1 E280A Autosomal Dominant Alzheimer's Disease Kindred: a Cross-sectional Study." The Lancet. Neurology, vol. 11, no. 12, 2012, pp. 1057-65.
Fleisher AS, Chen K, Quiroz YT, et al. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurol. 2012;11(12):1057-65.
Fleisher, A. S., Chen, K., Quiroz, Y. T., Jakimovich, L. J., Gomez, M. G., Langois, C. M., Langbaum, J. B., Ayutyanont, N., Roontiva, A., Thiyyagura, P., Lee, W., Mo, H., Lopez, L., Moreno, S., Acosta-Baena, N., Giraldo, M., Garcia, G., Reiman, R. A., Huentelman, M. J., ... Reiman, E. M. (2012). Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. The Lancet. Neurology, 11(12), 1057-65. https://doi.org/10.1016/S1474-4422(12)70227-2
Fleisher AS, et al. Florbetapir PET Analysis of Amyloid-β Deposition in the Presenilin 1 E280A Autosomal Dominant Alzheimer's Disease Kindred: a Cross-sectional Study. Lancet Neurol. 2012;11(12):1057-65. PubMed PMID: 23137949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. AU - Fleisher,Adam S, AU - Chen,Kewei, AU - Quiroz,Yakeel T, AU - Jakimovich,Laura J, AU - Gomez,Madelyn Gutierrez, AU - Langois,Carolyn M, AU - Langbaum,Jessica B S, AU - Ayutyanont,Napatkamon, AU - Roontiva,Auttawut, AU - Thiyyagura,Pradeep, AU - Lee,Wendy, AU - Mo,Hua, AU - Lopez,Liliana, AU - Moreno,Sonia, AU - Acosta-Baena,Natalia, AU - Giraldo,Margarita, AU - Garcia,Gloria, AU - Reiman,Rebecca A, AU - Huentelman,Matthew J, AU - Kosik,Kenneth S, AU - Tariot,Pierre N, AU - Lopera,Francisco, AU - Reiman,Eric M, Y1 - 2012/11/06/ PY - 2012/11/10/entrez PY - 2012/11/10/pubmed PY - 2013/1/19/medline SP - 1057 EP - 65 JF - The Lancet. Neurology JO - Lancet Neurol VL - 11 IS - 12 N2 - BACKGROUND: Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimer's disease. By assessing the accumulation of Aβ in people at risk of genetic forms of Alzheimer's disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease. METHODS: Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer's disease Colombian kindred aged 18-60 years were recruited from the Alzheimer's Prevention Initiative's registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimer's Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions.was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition. FINDINGS: We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3-33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. (18)F florbetapir binding rose steeply over the next 9·4 years and plateaued at a mean age of 37·6 years (95% CI 35·3-40·2), about 6 and 11 years before the expected respective median ages at mild cognitive impairment and dementia onset. Prominent florbetapir binding was seen in the anterior and posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as well as in the basal ganglia. Binding in the basal ganglia was not seen earlier or more prominently than in other regions. INTERPRETATION: These findings contribute to the understanding of preclinical familial Alzheimer's disease and help set the stage for assessment of amyloid-modifying treatments in the prevention of familial Alzheimer's disease. FUNDING: Avid Radiopharmaceuticals, Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona. SN - 1474-4465 UR - https://www.unboundmedicine.com/medline/citation/23137949/Florbetapir_PET_analysis_of_amyloid_β_deposition_in_the_presenilin_1_E280A_autosomal_dominant_Alzheimer's_disease_kindred:_a_cross_sectional_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(12)70227-2 DB - PRIME DP - Unbound Medicine ER -