Impact of thyroid hormone perturbations in adult mice: brain weight and blood vessel changes, gene expression variation, and neurobehavioral outcomes.

Mouse models of hyper- and hypothyroidism were used to examine the effects of thyroid hormone (TH) dyshomeostasis on the aging mammalian brain. 13-14 month-old mice were treated for 4months with either levothyroxine (hyperthyroid) or a propylthiouracil and methimazole combination (PTU/Met; hypothyroid). Hyperthyroid mice performed better on Morris Water Maze than control mice, while hypothyroid mice performed worse.

Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene.

We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n = 119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex.

Synaptic change in the posterior cingulate gyrus in the progression of Alzheimer's disease.

Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer's disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology.

Synapse stability in the precuneus early in the progression of Alzheimer's disease.

Amnestic mild cognitive impairment (aMCI) is considered to be one of the early stages in the progression from no cognitive impairment (NCI) to Alzheimer's disease (AD). Individuals with aMCI have increased levels of AD-type neuropathology in multiple regions of the neocortex and hippocampus and demonstrate a loss of synaptic connectivity. Recent neuroimaging studies have reported increased levels of 11C-PiB (Pittsburgh, compound B) in regions of the neocortex including the precuneus region of the medial parietal lobe.

Synaptic loss in the inferior temporal gyrus in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) is a slowly progressing form of dementia characterized in its earliest stages as a loss of memory. Individuals with amnestic mild cognitive impairment (aMCI) may be in the earliest stages of the disease and represent an opportunity to identify pathological changes related to the progression of AD. Synaptic loss is one of the hallmarks of AD and associated with cognitive impairment.

Alzheimer's disease-related alterations in synaptic density: neocortex and hippocampus.

Alzheimer's disease (AD) is a progressive disorder that is characterized by the accumulation of neuropathologic lesions and neurochemical alterations. Ultrastructural investigations in many association regions of the neocortex and the hippocampal dentate gyrus have demonstrated a disease-related decline in numerical synaptic density. This decline in brain connectivity occurs early in the disease process and strongly correlates with the cognitive decline observed in AD.

Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment.

One of the major neuropathological findings in the brains of individuals with Alzheimer's disease (AD) is a loss of synaptic contacts in both the neocortex and hippocampus. Here we report, for the first time, an estimate of the total number of synapses in the outer molecular layer (OML) of the human dentate gyrus, in individuals with early Alzheimer's disease (eAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI). An unbiased stereologic sampling scheme coupled with transmission electron microscopy to directly visualize synaptic contacts, was used to estimate the total number of synapses in short postmortem autopsy tissue.

Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies.

Morphologic studies of the neuropathology in Alzheimer's disease (AD) have demonstrated significant loss of synaptic connectivity in many regions of the neocortex and hippocampus. The strongest correlation with cognitive decline in AD is with the synaptic density. This article discusses the ultrastructural studies that have documented changes in synaptic numbers in many areas of association cortex and in the hippocampal dentate gyrus molecular layer.

Alzheimer's disease-related synapse loss in the cingulate cortex.

Synapse loss is considered a profound neuropathology associated with Alzheimer's disease (AD). This AD-related change in connectivity can be demonstrated in many regions of the neocortex. The posterior cingulate cortex has been identified as an area involved early in the disease process but has not been well studied.