Rizwan S Akhtar1, Sharon X Xie2, Laura Brennan3, Michael J Pontecorvo4, Howard I Hurtig5, John Q Trojanowski6, Daniel Weintraub3, Andrew D Siderowf7. 1. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA; Center for Neurodegenerative Disease Research and Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA. 2. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA. 3. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA; Department of Psychiatry, Perelman School of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA. 4. Avid Radiopharmaceuticals, Philadelphia, PA 19104, USA. 5. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA. 6. Center for Neurodegenerative Disease Research and Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA. 7. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3339, USA; Avid Radiopharmaceuticals, Philadelphia, PA 19104, USA.
Abstract
BACKGROUND: Neuronal loss and α-synuclein (α-syn) pathology are diagnostic of PD in the appropriate clinical context. However, some PD patients have co-morbid Alzheimer's disease (AD) pathology on autopsy, including amyloid-β (Aβ) plaques and neurofibrillary tangles. Florbetapir(18F) is a PET ligand that detects Aβ pathology. We hypothesized that florbetapir(18F) imaging could detect Aβ pathology in Parkinson disease dementia (PDD) patients prior to death. OBJECTIVE: To determine the utility of florbetapir(18F) PET imaging in detecting Aβ pathology in patients with autopsy-confirmed PDD. METHODS: Five participants with PDD had florbetapir(18F) PET imaging prior to death as a part of a longitudinal research study of cognitive decline in PD. PET scans were evaluated by expert raters blinded to clinical and neuropathological information. At autopsy, all five participants underwent semi-quantitative assessments of regional Aβ and tau immunohistochemistry. RESULTS: All participants met neuropathological criteria for PD. Two had both positive florbetapir(18F) scans and Aβ-positive plaques in multiple brain regions. Regional florbetapir(18F) binding correlated with regional semi-quantitative Aβ pathology in these cases. Three cases had negative florbetapir(18F) scans. Two of these had significant tau pathology without Aβ pathology, consistent with progressive supranuclear palsy (PSP) in one case and argyrophilic grain disease (AGD) in the other. The last case had a low level of AD neuropathological change. CONCLUSIONS: Florbetapir(18F) Aβ imaging can detect the presence of Aβ neuropathology in patients with PDD. This imaging technique may aid the clinical evaluation of PDD patients to determine if cognitive decline is occurring in the setting of Aβ accumulation.
BACKGROUND:Neuronal loss and α-synuclein (α-syn) pathology are diagnostic of PD in the appropriate clinical context. However, some PDpatients have co-morbid Alzheimer's disease (AD) pathology on autopsy, including amyloid-β (Aβ) plaques and neurofibrillary tangles. Florbetapir(18F) is a PET ligand that detects Aβ pathology. We hypothesized that florbetapir(18F) imaging could detect Aβ pathology in Parkinson disease dementia (PDD) patients prior to death. OBJECTIVE: To determine the utility of florbetapir(18F) PET imaging in detecting Aβ pathology in patients with autopsy-confirmed PDD. METHODS: Five participants with PDD had florbetapir(18F) PET imaging prior to death as a part of a longitudinal research study of cognitive decline in PD. PET scans were evaluated by expert raters blinded to clinical and neuropathological information. At autopsy, all five participants underwent semi-quantitative assessments of regional Aβ and tau immunohistochemistry. RESULTS: All participants met neuropathological criteria for PD. Two had both positive florbetapir(18F) scans and Aβ-positive plaques in multiple brain regions. Regional florbetapir(18F) binding correlated with regional semi-quantitative Aβ pathology in these cases. Three cases had negative florbetapir(18F) scans. Two of these had significant tau pathology without Aβ pathology, consistent with progressive supranuclear palsy (PSP) in one case and argyrophilic grain disease (AGD) in the other. The last case had a low level of AD neuropathological change. CONCLUSIONS:Florbetapir(18F) Aβ imaging can detect the presence of Aβ neuropathology in patients with PDD. This imaging technique may aid the clinical evaluation of PDDpatients to determine if cognitive decline is occurring in the setting of Aβ accumulation.
Authors: H I Hurtig; J Q Trojanowski; J Galvin; D Ewbank; M L Schmidt; V M Lee; C M Clark; G Glosser; M B Stern; S M Gollomp; S E Arnold Journal: Neurology Date: 2000-05-23 Impact factor: 9.910
Authors: Kejal Kantarci; Val J Lowe; Bradley F Boeve; Stephen D Weigand; Matthew L Senjem; Scott A Przybelski; Dennis W Dickson; Joseph E Parisi; David S Knopman; Glenn E Smith; Tanis J Ferman; Ronald C Petersen; Clifford R Jack Journal: Neurobiol Aging Date: 2011-10-21 Impact factor: 4.673
Authors: S N Gomperts; D M Rentz; E Moran; J A Becker; J J Locascio; W E Klunk; C A Mathis; D R Elmaleh; T Shoup; A J Fischman; B T Hyman; J H Growdon; K A Johnson Journal: Neurology Date: 2008-09-16 Impact factor: 9.910
Authors: Susan M Landau; Christopher Breault; Abhinay D Joshi; Michael Pontecorvo; Chester A Mathis; William J Jagust; Mark A Mintun Journal: J Nucl Med Date: 2012-11-19 Impact factor: 10.057
Authors: Brittany N Dugger; Christopher M Clark; Geidy Serrano; Monica Mariner; Barry J Bedell; R Edward Coleman; P Murali Doraiswamy; Ming Lu; Adam S Fleisher; Eric M Reiman; Marwan N Sabbagh; Carl H Sadowsky; Julie A Schneider; Simone P Zehntner; Alan P Carpenter; Abhinay D Joshi; Mark A Mintun; Michael J Pontecorvo; Daniel M Skovronsky; Lucia I Sue; Thomas G Beach Journal: J Neuropathol Exp Neurol Date: 2014-01 Impact factor: 3.685
Authors: Glenn T Stebbins; Christopher G Goetz; David J Burn; Joseph Jankovic; Tien K Khoo; Barbara C Tilley Journal: Mov Disord Date: 2013-02-13 Impact factor: 10.338
Authors: Jon B Toledo; Vivianna M Van Deerlin; Edward B Lee; EunRan Suh; Young Baek; John L Robinson; Sharon X Xie; Jennifer McBride; Elisabeth M Wood; Theresa Schuck; David J Irwin; Rachel G Gross; Howard Hurtig; Leo McCluskey; Lauren Elman; Jason Karlawish; Gerard Schellenberg; Alice Chen-Plotkin; David Wolk; Murray Grossman; Steven E Arnold; Leslie M Shaw; Virginia M-Y Lee; John Q Trojanowski Journal: Alzheimers Dement Date: 2013-08-24 Impact factor: 21.566
Authors: Andrew Siderowf; Michael J Pontecorvo; Holly A Shill; Mark A Mintun; Anupa Arora; Abhinay D Joshi; Ming Lu; Charles H Adler; Douglas Galasko; Carolyn Liebsack; Daniel M Skovronsky; Marwan N Sabbagh Journal: BMC Neurol Date: 2014-04-09 Impact factor: 2.474
Authors: Julia Shirvan; Nathan Clement; Rong Ye; Samantha Katz; Aaron Schultz; Keith A Johnson; Teresa Gomez-Isla; Matthew Frosch; John H Growdon; Stephen N Gomperts Journal: Neurology Date: 2019-06-26 Impact factor: 9.910
Authors: Rizwan S Akhtar; Sharon X Xie; Yin J Chen; Jacqueline Rick; Rachel G Gross; Ilya M Nasrallah; Vivianna M Van Deerlin; John Q Trojanowski; Alice S Chen-Plotkin; Howard I Hurtig; Andrew D Siderowf; Jacob G Dubroff; Daniel Weintraub Journal: PLoS One Date: 2017-05-25 Impact factor: 3.240
Authors: Carme Uribe; Barbara Segura; Hugo C Baggio; Alexandra Abos; Anna I Garcia-Diaz; Anna Campabadal; Maria J Marti; Francesc Valldeoriola; Yaroslau Compta; Nuria Bargallo; Carme Junque Journal: Front Aging Neurosci Date: 2018-03-27 Impact factor: 5.750