Thus, AT8 and PHF-1 lots reflect neuritic degeneration rather than intracellular NFT. Open in a separate window Open in a separate window Fig. A survey of the entire cingulated gyrus showed a wide dispersion of A42 with the AZ1 highest concentration in the perigenual part of the anterior cingulate cortex; A appeared to be linked with neuron loss and did not overlap with the heaviest neuritic degeneration. The current case may represent a nonmemory presentation AZ1 of mild cognitive impairment (executive mild cognitive impairment) that is associated with frontal and anterior cingulate pathology and may be an early stage of the frontal variant of Alzheimer disease. strong class=”kwd-title” Keywords: Isolated executive impairment, Cortical neurofibrillary tangles, Amyloid peptides, Cingulate gyrus, Mild cognitive impairment Introduction Cognitive impairment in the absence of dementia in individuals over age 65 is 2C5 times more common AZ1 than dementia . To date, isolated memory impairment has been the primary focus of these studies. The term mild cognitive impairment (MCI) is commonly used to categorize nondemented elderly who exhibit isolated memory impairment and a relative preservation of other cognitive domains and activities of daily living . Individuals with MCI are at an increased risk for Alzheimer disease (AD) . Despite the focus on memory Mouse monoclonal antibody to Placental alkaline phosphatase (PLAP). There are at least four distinct but related alkaline phosphatases: intestinal, placental, placentallike,and liver/bone/kidney (tissue non-specific). The first three are located together onchromosome 2 while the tissue non-specific form is located on chromosome 1. The product ofthis gene is a membrane bound glycosylated enzyme, also referred to as the heat stable form,that is expressed primarily in the placenta although it is closely related to the intestinal form ofthe enzyme as well as to the placental-like form. The coding sequence for this form of alkalinephosphatase is unique in that the 3 untranslated region contains multiple copies of an Alu familyrepeat. In addition, this gene is polymorphic and three common alleles (type 1, type 2 and type3) for this form of alkaline phosphatase have been well characterized impairment, the clinical outcome of isolated impairment in other cognitive domains such as executive function is not known. The current study describes a nondemented elderly subject with isolated executive impairment and preserved memory function. Methods We evaluated a 68-year-old female with 16 years of education as part of a longitudinal study of healthy elderly. She completed one neuropsychological evaluation (table 1). No brain MRI was performed. Her medical history included tonsillectomy, coronary artery disease, hypertension, and hypercholesterolemia. Her social history included occasional alcohol use, and she had smoked 1/3 pack of cigarettes per day for 20 years. The subject died 20 months after the evaluation following an acute myocardial infarction. Table 1 Neuropsychological test results thead th align=”left” rowspan=”1″ colspan=”1″ MMSE /th th align=”left” rowspan=”1″ colspan=”1″ 29/30 /th /thead em Memory /em CERAD Word List Learning Task??Trial 17/10??Trial 28/10??Trial 38/10??5-min delayed recall8/10??5-min recognition20/10??30-min delayed recall8/10??30-min recognition20/10WMS-R Visual Reproductions??Immediate recall40/45 (99th percentile)??30-min delayed recall25/45 (67th percentile) hr / em Language /em Boston Naming Test C modified29/30CERAD Animal Naming18 hr / em Abstract reasoning /em WAIS-R similarities24 (scaled score 12) hr / em Visuospatial /em CERAD constructional praxis10/11WAIS-R block design24 (scaled score 11) hr / em Executive /em TMT-A79 (MOANS scaled score 3)TMT-B123 (MOANS scaled score 7) Open in a separate window MMSE = Mini-Mental State Exam; CERAD = Consortium to Establish a Registry for Alzheimer Disease; WMS-R = Wechsler Memory Scale C Revised; WAIS-R = Wechsler Adult Intelligence Scale C Revised; MOANS = Mayos Older Americans Normative Studies. Tissue Preparation and Diagnosis The postmortem interval was 8.5 h and the brain was removed and postfixed in 10% formalin. A standard neuropathological examination (R.K.) was performed for diagnostic purposes . Blocks from Brodmanns areas (BA) in the frontal cortex (BA6, 8, 9, 10, 11), entorhinal cortex (BA28), inferior parietal cortex (BA7), temporal cortex (BA22), and occipital cortex (BA17) were sectioned at 50 m using a vibratome. The left cingulate gyrus and adjacent cortex were removed following brain cutting into 1-cm slabs and the medial surface was reconstructed and photographed (fig. 2). The blocks were cryoprotected in graded sucrose and cut into 8 series of 50-m-thick sections on a cryostat. Open in a separate window Fig. 2 Reconstruction of the medial surface with the following structures: cc = Corpus callosum; cgs = cingulate sulcus; pcgs = paracingulate sulcus; spls = suprasplenial sulci; mr = marginal ramus of the cgs. A42-immunoreacted sections are shown from 7 levels in this and the next figure and each arrow in sections 2C7 marks an approximate border between AZ1 qualitatively low or high amounts of A42. Arabic numbers overlying each section are for cytoarchitectural areas. The boxes in sections 4 and 6 are of sections with high/low levels of A42 magnified below where the arrowheads show the borders between layers III/V and IV/V, respectively. Immunocytochemistry Antibodies to -amyloid (A1C17; 6E10, 1:5,000; Signet Laboratories) were used to label senile plaques (SP). Mature neurofibrillary tangles (NFT) were evaluated with PHF-1 (1:1,000, provided by Peter AZ1 Davies, Albert Einstein College of Medicine), and early NFT were analyzed with AT8 (1:10,000; Pierce Biotechnology). Sections immunostained for A were pretreated with 90% formic acid for 4 min. Cingulate cortex sections were reacted with A1C42 and 1C40 antibodies (Oncogene Research) and AT8 (Innogenetics), and a separate series of sections was stained with thionine. Image Analysis Ten individual 525-by-410-m fields in 5 superficial cortical layers and 5 deep cortical layers adjacent to white matter were digitized for each brain region. The proportion of area.