Journal of Alzheimer's Disease - Volume 47, issue 3

Authors: Caroppo, Paola | Habert, Marie-Odile | Durrleman, Stanley | Funkiewiez, Aurélie | Perlbarg, Vincent | Hahn, Valérie | Bertin, Hugo | Gaubert, Malo | Routier, Alexandre | Hannequin, Didier | Deramecourt, Vincent | Pasquier, Florence | Rivaud-Pechoux, Sophie | Vercelletto, Martine | Edouart, Geoffrey | Valabregue, Romain | Lejeune, Pascal | Didic, Mira | Corvol, Jean-Christophe | Benali, Habib | Lehericy, Stephane | Dubois, Bruno | Colliot, Olivier | Brice, Alexis | Le Ber, Isabelle | the Predict-PGRN study group

Article Type: Research Article

Abstract: The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+ ) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in …the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n  = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset. Show more

Keywords: Cortical thickness, dementia, frontotemporal dementia, frontotemporal lobar degeneration, GRN, longitudinal, preclinical study, presymptomatic, progranulin, PET

DOI: 10.3233/JAD-150270

Citation: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 751-759, 2015

Authors: Bradley-Whitman, Melissa A. | Abner, Erin | Lynn, Bert C. | Lovell, Mark A.

Article Type: Research Article

Abstract: Specific biomarkers in a readily accessible biological fluid, such as blood, could aid in the identification, characterization, validation, and routine monitoring of Alzheimer’s disease (AD) progression. In the current study, levels of the previously described novel cerebrospinal fluid aberrant protein complex composed of prostaglandin-D-synthase (PDS) and transthyretin (TTR) were quantified in plasma by a custom two-probe sandwich ELISA and compared to amyloid-β (Aβ)1-42 as a standard plasma biomarker of AD. Plasma was analyzed from 140 probable AD subjects, 135 subjects with mild cognitive impairment (MCI), 74 normal control subjects (NC) prior to MCI transition, 23 diseased control (DC) subjects …with either frontotemporal dementia or dementia with Lewy bodies, and 182 normal control (NC) subjects who did not progress to MCI or dementia. Levels of Aβ 1-42 were significantly elevated in NC subjects prior to MCI conversion but significantly reduced in probable AD subjects compared to NC subjects. Similarly, levels of the PDS-TTR complex were significantly reduced in both MCI and probable AD subjects compared to NC subjects. Furthermore, levels of Aβ 1-42 and the PDS-TTR complex were not significantly different in DC subjects compared to NC subjects. MMSE scores were weakly but significantly correlated with plasma levels of the PDS-TTR complex and Aβ 1-42 . Trail B scores were weakly but significantly correlated with plasma levels of Aβ 1-42 . Comparison of receiver operating curves shows the PDS-TTR complex is comparable to Aβ 1-42 in both MCI and probable AD subjects. Show more

Keywords: Alzheimer’s disease, biomarker, PDS-TTR complex, plasma

DOI: 10.3233/JAD-150183

Citation: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 761-771, 2015

Authors: Valotassiou, Varvara | Papatriantafyllou, John | Sifakis, Nikolaos | Tzavara, Chara | Tsougos, Ioannis | Psimadas, Dimitrios | Fezoulidis, Ioannis | Kapsalaki, Eftychia | Hadjigeorgiou, George | Georgoulias, Panagiotis

Article Type: Research Article

Abstract: Early diagnosis of Alzheimer’s disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99m Tc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGamTM ) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software’s normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9±8.1 years, …mean Mini-Mental State Examination 22.6±2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD. Show more

Keywords: Brain perfusion imaging, Brodmann areas, mild Alzheimer’s disease, SPECT

DOI: 10.3233/JAD-150068

Citation: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 773-785, 2015

Article Type: Meeting Report

DOI: 10.3233/JAD-150461

Citation: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 787-791, 2015