%0 Journal Article %J J Alzheimers Dis %D 2018 %T Antemortem-Postmortem Correlation of Florbetapir (18F) PET Amyloid Imaging with Quantitative Biochemical Measures of Aβ42 but not Aβ40. %A Beach, Thomas G %A Maarouf, Chera L %A Intorcia, Anthony %A Sue, Lucia I %A Serrano, Geidy E %A Lu, Ming %A Joshi, Abhinay %A Pontecorvo, Michael J %A Roher, Alex E %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Amyloidosis %K Aniline Compounds %K Autopsy %K Brain %K Ethylene Glycols %K Humans %K Linear Models %K Peptide Fragments %K Plaque, Amyloid %K Positron-Emission Tomography %X

Amyloid imaging demonstrates the in vivo presence of amyloid-β (Aβ) deposits in the aging human brain but it is still unknown which structural forms and modifications of Aβ are detected. In Alzheimer's disease, most amyloid deposits are predominantly composed of Aβ ending at amino acid residues Val40 or Ala42. It has been reported that Aβ40 is largely restricted to neuritic plaques while Aβ42 may be deposited in amyloid plaques of all types, and is often the sole component of diffuse plaques. The distinction is important as it is mainly the neuritic plaques that correlate with cognitive impairment while diffuse plaques may be the initial type of Aβ deposited. Whether PET amyloid ligands such as florbetapir-18F (Amyvid) are partially or wholly selective for brain deposits of Aβ40 or Aβ42 is currently unknown. We compared antemortem florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with postmortem biochemical (ELISA) measurements employing specific antibodies against Aβ40 and Aβ42. Spearman's univariable correlations were significant for both Aβ40 and Aβ42, but were much stronger for Aβ42. Multiple linear regression showed significance only for Aβ42. These results suggest that florbetapir binds only weakly, if at all, to Aβ40. This may be in part due to the higher likelihood for Aβ42 to be present in a β-pleated sheet tertiary structure, or to differences between Aβ40 and Aβ42 in β-pleated sheet tertiary or quaternary structure.

%B J Alzheimers Dis %V 61 %P 1509-1516 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29376867?dopt=Abstract %R 10.3233/JAD-170762 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Familial Presenilin Mutations and Sporadic Alzheimer's Disease Pathology: Is the Assumption of Biochemical Equivalence Justified? %A Roher, Alex E %A Maarouf, Chera L %A Kokjohn, Tyler A %K Alzheimer Disease %K Amyloid beta-Peptides %K Brain %K Humans %K Mutation %K Presenilins %X

Studies of presenilin (PSEN) gene mutations producing early onset Alzheimer's disease (AD) have helped elucidate the pathogenic mechanisms of dementia and guided clinical trials of potential therapeutic interventions. Although familial and sporadic forms of AD share features, it is unclear if the two are precisely equivalent. In addition, PSEN mutations do not all produce a single phenotype, but exhibit substantial variability in clinical manifestations, which are related to the position and chemical nature of their amino acid substitutions as well as ratios of critical molecules such as Aβ40 and Aβ42. These differences complicate the interpretation of critical clinical trial results and their desired extrapolation to sporadic AD treatment. In this perspective, we examine differences between familial AD and sporadic AD as well as attributes shared by these uniquely arising disturbances in brain biochemical homeostasis that culminate in dementia.

%B J Alzheimers Dis %V 50 %P 645-58 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26757189?dopt=Abstract %R 10.3233/JAD-150757 %0 Journal Article %J J Alzheimers Dis %D 2016 %T The Presence of Select Tau Species in Human Peripheral Tissues and Their Relation to Alzheimer's Disease. %A Dugger, Brittany N %A Whiteside, Charisse M %A Maarouf, Chera L %A Walker, Douglas G %A Beach, Thomas G %A Sue, Lucia I %A Garcia, Angelica %A Dunckley, Travis %A Meechoovet, Bessie %A Reiman, Eric M %A Roher, Alex E %K Aged %K Aged, 80 and over %K Aging %K Alzheimer Disease %K Blotting, Western %K Colon %K Enzyme-Linked Immunosorbent Assay %K Female %K Frontal Lobe %K Gray Matter %K Humans %K Immunohistochemistry %K Liver %K Male %K Neurofibrillary Tangles %K Phosphorylation %K Severity of Illness Index %K Sex Characteristics %K Skin %K Submandibular Gland %K tau Proteins %X

Tau becomes excessively phosphorylated in Alzheimer's disease (AD) and is widely studied within the brain. Further examination of the extent and types of tau present in peripheral tissues and their relation to AD is warranted given recent publications on pathologic spreading. Cases were selected based on the presence of pathological tau spinal cord deposits (n = 18). Tissue samples from sigmoid colon, scalp, abdominal skin, liver, and submandibular gland were analyzed by western blot and enzyme-linked immunosorbent assays (ELISAs) for certain tau species; frontal cortex gray matter was used for comparison. ELISAs revealed brain to have the highest total tau levels, followed by submandibular gland, sigmoid colon, liver, scalp, and abdominal skin. Western blots with antibodies recognizing tau phosphorylated at threonine 231(pT231), serine 396 and 404 (PHF-1), and an unmodified total human tau between residues 159 and 163 (HT7) revealed multiple banding patterns, some of which predominated in peripheral tissues. As submandibular gland had the highest levels of peripheral tau, a second set of submandibular gland samples were analyzed (n = 36; 19 AD, 17 non-demented controls). ELISAs revealed significantly lower levels of pS396 (p = 0.009) and pT231 (p = 0.005) in AD cases but not total tau (p = 0.18). Furthermore, pT231 levels in submandibular gland inversely correlated with Braak neurofibrillary tangle stage (p = 0.04), after adjusting for age at death, gender, and postmortem interval. These results provide evidence that certain tau species are present in peripheral tissues. Of potential importance, submandibular gland pT231 is progressively less abundant with increasing Braak neurofibrillary tangle stage.

%B J Alzheimers Dis %V 51 %P 345-56 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26890756?dopt=Abstract %R 10.3233/JAD-150859