Identification and validation of Alzheimer’s disease‐related metabolic pattern in patients with pathologically confirmed Alzheimer’s disease

Background Alzheimer’s disease (AD) is marked by accumulation of Aβ and tau protein causing neurodegeneration in the brain. AD represents a pathological and clinical continuum, ranging from mild cognitive impairment (MCI) to dementia. A specific metabolic imaging biomarker of AD ‐ Alzheimer’s disease‐related pattern (ADRP) has been previously identified from 2‐[ 18 F]fluorodeoxyglucose positron emission tomography (2‐[ 18 F]FDG‐PET) scans of clinically diagnosed AD patients, using scaled subprofile model based on principal component analysis (SSM/PCA) 1–3 . However the clinical diagnosis may be wrong in substantial number of cases 4 . We aimed to identify ADRP on patients with Alzheimer’s pathological changes in cerebrospinal (CSF) fluid and to validate it in an independent group of AD and other dementia patients and compare it to the original ADRP 1 . Method 2‐[ 18 F]FDG‐PET scans from 20 AD1 and 20 normal controls (NC1) were used for pattern identification. Additional 110 scans were analyzed for validation: 68 from AD patients (37 AD2, 13 atypical clinical presentation AD (atAD), 18 MCI), 21 with frontotemporal dementia (FTD), 8 non‐AD MCI and 13 NC2 (Table 1). AD was defined with CSF biomarkers as: Aβ42 < 815 pg/ml, pTau > 60 pg/ml, tTau > 400 pg/ml. Topographic profile rating algorithm was used to prospectively calculate ADRP Z‐scores from subjects scans 3 . Mini‐mental state examination (MMSE) was performed in all patients. Results ADRP was identified and voxel weights were found to be stable by bootstrap resampling, Figure 1. Pattern’s expression was significantly higher in AD1 than NC1 ( p <0.001) and it strongly correlated ( r =‐0.70) with MMSE. Pattern’s expression was also higher in AD2 than NC2 ( p <0.001), MCI vs. NC2 ( p <0.001), MCI vs. non‐AD MCI ( p =0.02) and AD2 vs. FTD ( p =0.02), Figure 2. Newly identified pattern moderately correlated ( r =0.52) with the original one 1 . Conclusions We identified ADRP on a cohort of pathologically confirmed AD patients, which was not done before. ADRP has shown to be a reliable metabolic biomarker of AD related neurodegeneration. References: (1) Mattis,PJ. et al. Neurology 87,1925–33(2016); (2) Teune,LK. et al. Curr Alzheimer Res 11,725–32(2014); (3) Spetsieris,PG. & Eidelberg,D. Neuroimage 54,2899–914(2011); (4) Beach,TG. et al . J. Neuropathol. Exp. Neurol . 71,266–273(2012).