Kurt A. Jellinger

Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

Abstract Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. &bgr;-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective forunderstanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of A&bgr; plaques and neurofibrillary tangles. Although A&bgr; plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.

PART, a distinct tauopathy, different from classical sporadic Alzheimer disease

The relationship between primary age-related tauopathy (PART) and Alzheimer’s disease (AD) is currently a matter of discussion. Recently the term PART was referred to cases characterized by mainly allocortical neurofibrillary (NF) pathology (Braak stages 0–IV) with only few or no amyloid (Aβ) deposits (Thal Aβ phases 0–2) [49]. In addition, no elevated soluble Aβ was detected in this disorder [9, 46]. PART cases that lack any Aβ do not meet formal criteria for sporadic AD according to the NIA–AA guidelines [35]. These neurofibrillary tangle (NFT)+/Aβ-brains are commonly observed in extreme old age [9, 15, 19]. When associated with a high density of NFTs in the same distribution and some cognitive deficits, the disorder has been referred to as tangle-predominant senile dementia (TPSD) [27] or “tangle-only dementia” [55].

In memoriam: Franz Seitelberger (1916–2007)

In the present year, the international neuroscience community has lost two of its most important personalities who, due to a unique combination of intelligence, charismatic leadership and extraordinary research capacities, have made major contributions to the development of modern neuropathology and brain research: 6 months after his friend Igor Klatzo’s death, Franz Seitelberger faded away after long and severe illness. About 21 years ago, a special issue of Acta Neuropathologica was dedicated to his 70th birthday, and as one of his oldest scholars and friends, the present author had the privilege to write the introduction and laudatio. Franz Seitelberger was born in Vienna, Austria, on December 4, 1916. After graduating from Vienna University School of Medicine in 1940, he started his medical career in a neurological hospital in Vienna and later in the special department for brain and nerve injuries at Bad Ischl, headed by the famous neurosurgeon Wilhelm Tönnis. From 1947, Seitelberger worked with Erwin Stransky and later, with Hans HoV, at the Neurological Hospital “Rosenhügel” in Vienna, and was registered as neurologist and psychiatrist in 1950. A year later, he began to work at the Neurological (Obersteiner) Institute of Vienna University School of Medicine, then headed by Hans HoV. In 1953, he accepted the opportunity to work with Julius Hallervorden at the Department of Neuropathology of the Max-Planck Institute for Brain Research in Giessen, Germany. During this period he developed a special interest in diVuse sclerosis, neuroaxonal dystrophy, and other neurodegenerative and metabolic disorders. In 1954 he became docent (reader) in neurology, neuroanatomy and neuropathology, and in 1958 was nominated extraordinary professor. In 1959 Seitelberger was appointed director of the Obersteiner Institute which, after World War II, he completely reorganized and converted it into a modern research institute for both diagnostic and experimental neuropathology and neurosciences that soon achieved international reputation. He remained director of this important research institution until his retirement in 1987, which is now the Clinical Institute of Neurology of the Medical University of Vienna (headed by H. Budka). In 1960, he spent several months as visiting scientist at the National Institute for Neurological Diseases and Blindness (NINDB) in Bethesda, MD, USA, where he worked with Igor Klatzo on brain edema. In 1964 Seitelberger was appointed Full Professor of Neurology at Vienna University School of Medicine. In 1961, Acta Neuropathologica was founded as the organ of the Commissions (later Research Groups) of Neuropathology, Comparative Neuropathology, and Neurooncology of the World Federation of Neurology (WFN). Franz Seitelberger, one of the founders, was the Wrst Managing Editor of this K. A. Jellinger (&) Institute of Clinical Neurobiology, Medical University of Vienna, Kenyongasse 18, Vienna 1070, Austria e-mail: kurt.jellinger@univie.ac.at