Imaging the Earliest Stages of Alzheimers Disease

Abstract

Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimer's disease research, technical innovation has endowed us with a range of in vivo imaging techniques that promise to visualize Alzheimer' disease in living people. The earliest stage of Alzheimer's disease is characterized by cell-sickness, not cell-death, and can occur before the deposition of amyloid plaques or neurofibrillary tangles. In principle, 'functional' imaging techniques might be able to detect this early stage of the disease, a stage that was invisible to Alzheimer himself. Here, we will first define the neurobiological meaning of 'function' and then review the different approaches that measure brain dysfunction in Alzheimer' disease.

Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease

“…In the PFC, this included various molecular species from the ePC, SM, Sulf, and CE, whereas ERC displayed variability in ePC, PE, and TAG. Importantly, the differences in lipid signatures suggest that these two subregions encounter different aspects or stages of AD pathogenesis, as supported by functional and pathological analyses (19,20). As expected, neuronal loss was more obvious in the ERC than in the PFC (supplemental Dataset S3).…”

“…In this study, we present the lipidomic analysis of postmortem brain tissue obtained from patients with LOAD, specifically regions that typically are either moderately (prefrontal cortex, PFC) or severely (entorhinal cortex, ERC) affected in AD as well as a control region (cerebellum, CRB) that is largely unaffected by this disorder (19,20). We also provide the lipidome of forebrain tissue obtained from three commonly used transgenic mouse models of FAD, namely (i) PSEN1 M146V (PS1) (21), (ii) the Swedish mutant of APP K670N,M671L (APP) (22), and (iii) PS1-APP double transgenic (23) lines.…”

Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model

“…Within the MTL, the EC is an initial target in AD as significant loss of neurons in EC layer II occurs in the early stages of the disease [16,42]. Structural and functional imaging studies also show early, selective atrophy and hypometabolism in the EC of patients with mild cognitive impairment or early-stage AD [29,46,56]. The EC is divided into the medial (MEC) and lateral EC (LEC).…”

A review of β-amyloid neuroimaging in Alzheimer's disease

“…This can be measured by changes in cellular metabolic rate, which on a regional level can be visualized in vivo as changes in the metabolic demand reflected by decreased vascular perfusion and oxygen consumption (Wu and Small, 2006). Consequently there are a number of functional MRI (fMRI) studies that have assessed the consequence of neuropathology in terms of neuronal activity and connectivity.…”