Transneuronally altered dendritic processing of tangle-free neurons in Alzheimer's disease.
In Alzheimer's disease (AD), changes in dendritic morphology can be regarded as a result of an inherent disease-specific process associated with the formation of neurofibrillary tangles. Using three-dimensional morphometrical techniques and neuropatholologically staged tissue (Braak classification) of 32 cases, we demonstrate alterations in the dendritic length, branch order and number of segments of a tangle-free neuronal population in the AD-afflicted hippocampus, i.e. parvalbumin-containing cells of the fascia dentata. These alterations occurred primarily on the apical dendritic tree, the target of the entorhinal input. Mean of relative dendritic length, branch order and number of dendritic segments of apical dendrites decreased significantly, by 40-70% comparing stage V to stages 0 or I. In contrast, basal dendrites receiving no entorhinal input did not show significant changes. Entorhinal neurons projecting to the hippocampus are the first to be affected in AD and the first to die, resulting in hippocampal deafferentation. Therefore, this input-specific dendritic alteration of tangle-free neurons suggests that AD is confounded with a transneuronal component resulting from deafferentation. Experiments showed that deafferentation results in altered dendritic geometry causing an impaired signal integration. Thus, transneuronally altered dendritic signal integration might occur in neurons devoid of the major intraneuronal hallmark of AD, i.e. the neurofibrillary tangle.
Ohm
T G
TG
Institute of Anatomy, Charité, Humboldt-Universität, 10098 Berlin, Germany. thomas_georg.ohm@charite.de
Münch
S
S
Schönheit
B
B
Zarski
R
R
Nitsch
R
R
D000344:Afferent Pathways / Q000473:pathology* / Q000503:physiopathology; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D048429:Cell Size / Q000502:physiology; D003712:Dendrites / Q000473:pathology*; D018891:Dentate Gyrus / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010320:Parvalbumins / Q000378:metabolism
D010320:Parvalbumins