Essential tremor and Parkinson's disease: lack of a link.

Background: Essential tremor (ET) is a very common disorder and proving that there is a relationship to another common movement disorder, Parkinson's disease (PD), has been debated for years.

Methods: Review of the literature for links between ET and PD primarily focused on neuropathology as well as neurochemistry, epidemiology, genetics, olfactory function, and neuroimaging.

Results: While there may be some evidence to suggest an increase in occurrence of PD in people who were previously diagnosed with ET, neuropathologic studies of ET with similarly assessed control subjects do not find an increase in Lewy bodies in the ET group.

Reduced clinical and postmortem measures of cardiac pathology in subjects with advanced Alzheimer's Disease.

Background: Epidemiological studies indicate a statistical linkage between atherosclerotic vascular disease (ATH) and Alzheimer's disease (AD). Autopsy studies of cardiac disease in AD have been few and inconclusive. In this report, clinical and gross anatomic measures of cardiac disease were compared in deceased human subjects with and without AD.

Neuropathology and amyloid-β spectrum in a bapineuzumab immunotherapy recipient.

The field of Alzheimer's disease (AD) research eagerly awaits the results of a large number of Phase III clinical trials that are underway to investigate the effectiveness of anti-amyloid-β (Aβ) immunotherapy for AD. In this case report, we review the pertinent clinical history, examine the neuropathology, and characterize the Aβ profile of an AD patient who received bapineuzumab immunotherapy. The patient received four bapineuzumab infusions over a 39 week period.

Infiltration of T lymphocytes and expression of icam-1 in the hippocampus of patients with hippocampal sclerosis.

We and others have previously shown that reactive microglia express the major histocompatibility complex (MHC) class I and class II antigens in the hippocampus of patients suffering from epilepsy. Although the MHC glycoproteins serve as restriction elements for T lymphocytes, there is little information available regarding T lymphocytes in hippocampal sclerosis. In the present study, we investigated T lymphocyte infiltration in human hippocampi in four cases of epilepsy with hippocampal sclerosis, as well as in four control cases without neurological disease.

Use of florbetapir-PET for imaging beta-amyloid pathology.

Context: The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease.

Objective: To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy.

Design, Setting, And Participants: Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death used as the reference standard.

TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers.

Objectives: To determine whether TMEM106B single nucleotide polymorphisms (SNPs) are associated with frontotemporal lobar degeneration (FTLD) in patients with and without mutations in progranulin (GRN) and to determine whether TMEM106B modulates GRN expression.

Methods: We performed a case-control study of 3 SNPs in TMEM106B in 482 patients with clinical and 80 patients with pathologic FTLD-TAR DNA-binding protein 43 without GRN mutations, 78 patients with FTLD with GRN mutations, and 822 controls. Association analysis of TMEM106B with GRN plasma levels was performed in 1,013 controls and TMEM106B and GRN mRNA expression levels were correlated in peripheral blood samples from 33 patients with FTLD and 150 controls.

The biochemical aftermath of anti-amyloid immunotherapy.

Background: Active and passive immunotherapy in both amyloid-beta precursor protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid regression has been highly variable. Nine individuals with a clinical diagnosis of AD dementia were actively immunized with the Aβ peptide 1-42 (AN-1792) and subjected to detailed postmortem biochemical analyses. These patients were compared to 6 non-immunized AD cases and 5 non-demented control (NDC) cases.

PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.

Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE ε4 allele, the major late-onset Alzheimer's susceptibility gene.

In vivo PET imaging studies of young-adult carriers of the apolipoprotein E ε4 allele (APOEε4), the major Alzheimer's disease (AD) susceptibility gene, have demonstrated declines in glucose metabolism in brain areas later vulnerable to AD, such as posterior cingulate cortex, decades before the possible onset of symptoms. We have previously shown in postmortem studies that such metabolic declines in AD are associated with brain regional mitochondrial dysfunction. To determine whether young adult at-risk individuals demonstrate similar mitochondrial functional decline, we histochemically assessed postmortem tissues from the posterior cingulate cortex of young-adult carriers and noncarriers of APOEε4.

Postmortem interval effect on RNA and gene expression in human brain tissue.

Banked tissue is essential to the study of neurological disease but using postmortem tissue introduces a number of possible confounds. Foremost amongst these are factors relating to variation in postmortem interval (PMI). Currently there are conflicting reports on how PMI affects overall RNA integrity, and very few reports of how gene expression is affected by PMI.

Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders.

A sensitive immunohistochemical method for phosphorylated alpha-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson's disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer's disease with Lewy bodies (ADLB) and 17 with Alzheimer's disease with no Lewy bodies (ADNLB). The relative densities and frequencies of occurrence of phosphorylated alpha-synuclein histopathology (PASH) were tabulated and correlated with diagnostic category. The greatest densities and frequencies of PASH occurred in the spinal cord, followed by the paraspinal sympathetic ganglia, the vagus nerve, the gastrointestinal tract and endocrine organs.

Microglia activation and anti-inflammatory regulation in Alzheimer's disease.

Inflammatory regulators, including endogenous anti-inflammatory systems, can down-regulate inflammation thus providing negative feedback. Chronic inflammation can result from imbalance between levels of inflammatory mediators and regulators during immune responses. As a consequence, there are heightened inflammatory responses and irreversible tissue damage associated with many age-related chronic diseases.

Incidental Lewy body disease: clinical comparison to a control cohort.

Limited clinical information has been published on cases pathologically diagnosed with incidental Lewy body disease (ILBD). Standardized, longitudinal movement and cognitive data was collected on a cohort of subjects enrolled in the Sun Health Research Institute Brain and Body Donation Program. Of 277 autopsied subjects who had antemortem clinical evaluations within the previous 3 years, 76 did not have Parkinson's disease, a related disorder, or dementia of which 15 (20%) had ILBD.

Amyloid load in nondemented brains correlates with APOE e4.

179 Cognitively healthy adults enrolled in the Sun Health Brain Donation program between 7/91 and 12/07 were at least 60 years old and nondemented at the time of death (21 had developed mild cognitive impairment [MCI]). Amyloid plaque density, congophilic amyloid angiopathy (CAA), and neurofibrillary tangle (NFT) density scores were based on CERAD criteria and compared in apolipoprotein E (APOE) e4 carriers (n=42) and noncarriers (NC) (n=137). Mean age (83.

Whole genome association analysis shows that ACE is a risk factor for Alzheimer's disease and fails to replicate most candidates from Meta-analysis.

For late onset Alzheimer's disease (LOAD), the only confirmed, genetic association is with the apolipoprotein E (APOE) locus on chromosome 19. Meta-analysis is often employed to sort the true associations from the false positives. LOAD research has the advantage of a continuously updated meta-analysis of candidate gene association studies in the web-based AlzGene database.

Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer's disease.

The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer's disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included Abeta1-40, Abeta1-42, total tau, phosphorylated tau, alpha-1 acid glycoprotein (A1GP), haptoglobin, zinc alpha-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE).

Patients with Alzheimer disease have altered transmitral flow: echocardiographic analysis of the vortex formation time.

Objective: There is considerable epidemiologic evidence that Alzheimer disease (AD) is linked to cardiovascular risk factors and associated with an increased risk of symptomatic left ventricular (LV) dysfunction. Formation of a vortex alongside a diastolic jet signifies an efficient blood transport mechanism. The vortex formation time (VFT) is an index of optimal conditions for vortex formation.

Parkinson disease with dementia: comparing patients with and without Alzheimer pathology.

Subjects with Parkinson disease (PD) frequently develop dementia with greater than one-third meeting neuropathologic diagnostic criteria for Alzheimer disease (AD). The objective is to identify clinical and neuropathologic differences between Parkinson disease with dementia (PDD) subjects, with and without coexistent AD pathology. Neuropathologic examination was available on subjects diagnosed by clinicopathologic criteria with PDD-AD (N=23) and PDD+AD (N=28).

Correlation of clinical features with argyrophilic grains at autopsy.

Argyrophilic grains (AGs) are a pathologic feature found in association with neurodegenerative disease. Some have suggested that these features may occur as a distinctive condition. We reviewed 80 subjects from our tissue bank with pathologically confirmed AGs and identified their clinical features.

Functional, global and cognitive decline correlates to accumulation of Alzheimer's pathology in MCI and AD.

Background: Cognitive, global and functional instruments have been extensively investigated for correlations with neuropathological changes such as neurofibrillary tangles (NFTs), plaques, and synapse loss in the brain.

Objective: Our objective is to correlate the functional, global and cognitive decline assessed clinically with the neuropathological changes observed in a large prospectively characterized cohort of mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods: We examined 150 subjects (16 MCI and 134 AD) that were prospectively assessed and longitudinally followed to autopsy.

Proteomic analysis of Alzheimer's disease cerebrospinal fluid from neuropathologically diagnosed subjects.

A crucial need exists for reliable Alzheimer's disease (AD) diagnostic and prognostic tests. Given its intimate communication with the brain, the cerebrospinal fluid (CSF) has been surveyed intensively for reliable AD biomarkers. The heterogeneity of AD pathology and the unavoidable difficulties associated with the clinical diagnosis and differentiation of this dementia from other pathologies have confounded biomarker studies in antemortem CSF samples.