The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

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The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease

https://surfer.nmr.mgh.harvard.edu/ftp/articles/desikan06-parcellation.pdf

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...

Alzheimer's Disease: Genes, Proteins, and Therapy

Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.

http://science.sciencemag.org/content/sci/314/5796/130.full.pdf

Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Excitatory amino acid neurotransmitters, somatostatin and degenerate cortical neurons in Alzheimer's disease

Overview of frontotemporal dementia and the variety of its clinical presentations

By Joaquin M. Fuster. 1997. Pp. 352. Philadelphia: Lippincott-Raven.Price £60. ISBN 0-397-51849-8.

In the first edition of The Prefrontal Cortex the author set out his hypothesis concerning the functions of the prefrontal association cortex. These are conceived as being not modality specific but as integrative in nature, orchestrating the \`sensory' and \`motor' functions of the posterior and anterior association cortices in …

The prefrontal cortex.

Sex, mathematics, and the brain: An evolutionary perspective

We have examined chromatin in lymphocytes from patients with Alzheimer's disease (AD) and from normal individuals of a range of ages. We have found that the neucleosome repeat length does not vary with age for normal individuals over the range 24-78 years and that there is no difference between the value for AD cells (mean and standard deviation, 202 +/- 7 base pairs, bp) and for normals (207 +/- 5 bp). The rate of digestion of chromatin in lymphocyte nuclei by micrococcal nuclease does not appear to differ significantly between old and young normals and AD patients.

David Neary

Papers

Excitatory amino acid neurotransmitters, somatostatin and degenerate cortical neurons in Alzheimer's disease

Overview of frontotemporal dementia and the variety of its clinical presentations

The prefrontal cortex.

Sex, mathematics, and the brain: An evolutionary perspective

Characteristics of lymphocyte chromatin from Alzheimer's disease patients and from young and old normal individuals.