Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease

  title={Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease},
  author={Kurt A. Jellinger and Johannes Attems},
  journal={Acta Neuropathologica},
Neurofibrillary tangle predominant dementia (NFTPD) is a subset of late onset dementia, clinically different from traditional “plaque and tangle” Alzheimer disease (AD): later onset, shorter duration, less severe cognitive impairment, and almost absence of ApoE ε4. Neuropathology reveals abundant allocortical neurofibrillary pathology with no or few isocortical tau lesions, absence of neuritic plaques, absence or scarcity of amyloid deposits, but neurofibrillary changes comprising both 3 and 4… 
Commentary on the Paper "PART, a Distinct Tauopathy, Different from Classical Sporadic Alzheimer Disease"
NFTs in the absence of Aβ pathology are also common in cognitively intact elderly individuals, while some ApoE ε4 non-carriers with mild to moderate dementia may have extensive NFT pathology and minimal Aβ plaques.
Neuropathologically defined subtypes of Alzheimer’s disease differ significantly from neurofibrillary tangle-predominant dementia
While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.
Complex tauopathies versus tangle predominant dementia
It should be mentioned that many of the tangles in NFTD are extracellular ‘‘ghost’’ tangles, preferentially being immunoreactive for 3R tau, while intracellular tangles have a mixture of 3R and 4R t Tau, and ‘'pretangles'’ particularly occurring in limbic areas show 4RTau immunoreactivity.
Asymmetry of Hippocampal Tau Pathology in Primary Age-Related Tauopathy and Alzheimer Disease.
Evaluated asymmetry of neurofibrillary degeneration between left and right hippocampi in primary age-related tauopathy cases showed the importance of analyzing bilateral hippocampusi in the diagnostic evaluation of PART and potentially of other neurodegenerative diseases.
Primary age-related tauopathy (PART): a common pathology associated with human aging
A new term is recommended, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time.
Primary Age-Related Tauopathy (PART): Addressing the Spectrum of Neuronal Tauopathic Changes in the Aging Brain
Biomarker and ligand-based radiologic studies will be important to define PART antemortem and prospectively follow its natural history as it remains unclear whether PART is a distinct tauopathic entity separate from AD or rather represents an earlier histologic stage of AD.
Pathobiological Subtypes of Alzheimer Disease
  • K. Jellinger
  • Biology, Psychology
    Dementia and Geriatric Cognitive Disorders
  • 2020
Unraveling the heterogeneity among the AD spectrum entities is important for opening a window to pathogenic mechanisms affecting the brain and enabling precision medicine approaches as a basis for developing preventive and ultimately successful disease-modifying therapies for AD.
Neuropathology of the Alzheimer's continuum: an update
An up-to-date overview of AD neuropathology, its heterogeneity, and additional pathologies are provided in order to explain the difficulties in the diagnosis and the failure of clinical trials in AD patients.
The enigma of mixed dementia
Absence of α-synuclein pathology in postencephalitic parkinsonism
Neuropathologic examination of 10 brains with clinico-pathologically verified PEP confirmed widespread neurodegeneration in subcortical and brainstem areas associated with multifocal neurofibrillary pathology comprising both 3R and 4R tau.


Senile Dementia of the Neurofibrillary Tangle Type: A Comparison with Alzheimer’s Disease
The results indicate that the neurodegenerative process with NFT formation of the hippocampal region in SD-NFT would be different from that in AD.
Tau and α-synuclein brainstem pathology in Alzheimer disease: relation with extrapyramidal signs
Results suggest that neuronal loss in SN, partly related to tau lesions, is a major pathological substrate of EPS in AD, but some cases with and without EPS may show no or only minimal nigral changes.
Autosomal dominant dementia with widespread neurofibrillary tangles
A Midwestern American pedigree spanning four generations in which 15 individuals were affected by early‐onset dementia with long disease duration, with an autosomal dominant inheritance pattern, and with α‐rich neurofibrillary pathology found in the brain post mortem is presented.
Clinical Aspects of ‘Senile Dementia of the Tangle Type’ – A Subset of Dementia in the Senium Separable from Late-Onset Alzheimer’s Disease
There is a subset of dementia patients in the senium, in whom abundant neurofibrillary tangles (NFTs) are present mainly in the hippocampal region without significant numbers of senile plaques, which has been designated as senile dementia of the tangle type (SDT).
Senile dementia of the neurofibrillary tangle type (tangle‐only dementia): Neuropathological criteria and clinical guidelines for diagnosis *
  • M. Yamada
  • Psychology, Biology
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2003
Criteria for neuropathological diagnosis of SD‐NFT is proposed: (i) late‐onset dementia with abundant NFT in the hippocampal region and absence or scarcity of senile plaques throughout the brain; and (ii) exclusion of other dementias with NFT.
Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle‐only dementia): The Hisayama study
  • K. Noda, K. Sasaki, T. Iwaki
  • Psychology, Medicine
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2006
Although many previous papers have reported that the densities of NFT in the limbic system in SD‐NFT were significantly higher than those in AD, there was considerable overlap of N FT densities in CA1 among the non‐demented elderly, AD subjects and SD‐nFT subjects.
A subset of senile dementia with high incidence of the apolipoprotein E epsilon2 allele.
There is a subset of very elderly patients with senile dementia in whom abundant neurofibrillary tangles are present, mainly in the hippocampal region, without a significant number of senile plaques, which suggests that this type of dementia is distinct from Alzheimer's disease not only from a neuropathological but also from a genetic viewpoint.
Selective Neurofibrillary Degeneration of the Hippocampal CA2 Sector Is Associated with Four‐Repeat Tauopathies
24 atypical cases were identified, including four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease (AGD), and 19 of the 21 atypicals cases were pure or mixed cases of AGD.
Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia.
The low prevalence of the apoE epsilon 4 allele in this subset of patients is striking and suggests that NFT-predominant senile dementia is a dementing neurodegenerative disease in which the deposition of A beta-amyloid did not occur.
APOE E4 is a determinant for Alzheimer type pathology in progressive supranuclear palsy
Alzheimer type pathology was more frequent in women and older individuals with PSP, and 19 of the 40 patients with PSP with Alzheimer type pathology carried at least one APOE ε4 allele, which was significantly higher in PSP with AD or pathologic aging than in pure PSP.