Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS): Two diseases linked by TDP-43 Pathology

Conference Paper/Poster - Nov 4, 2011


Felbecker A, Brugger F, Tettenborn B, Sommacal A, Neumann M (2011). Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS): Two diseases linked by TDP-43 Pathology.
Conference Paper/Poster (English)
Conference Name
SNG Jahrestagung (St. Gallen)
Publisher Proceedings
Publication Date
Nov 4, 2011
Issn Print
Isbn Number
supplement 4 ad 2011;162(4), 10 S
Brief description/objective

Introduction: A subset of Frontotemporal Lobar Degeneration
(FTLD) patients develops signs of Amyotrophic Lateral Sclerosis
(ALS) during the course of the disease and – vice versa – some
patients with ALS show features of frontotemporal dementia.
Thus, a common pathological cause of these neurodegenerative
diseases has been subject of intensive research. Recently, TDP-
43 and FUS (Fused in Sarcoma Protein) have been identified as
disease proteins in both conditions confirming that they belong
to a clinico-pathological spectrum of diseases.
Case presentation: We report the case of a 53-year-old man
who developed behavioural changes over a course of
approximately 6 months, leading to massive problems at work
as a bank employee. Additionally, he showed changed sexual
behaviour and became unable to manage his finances.
According to history, clinical and neuropsychological features, a
diagnosis of behavioural variant of frontotemporal dementia was
established. Shortly after, the patient developed fasciculations
of both arms, followed by mild pareses mainly of the right arm.
During further follow-up, signs of motor neuron disease
deteriorated rapidly and ALS was diagnosed. Even though the
patient received best supportive treatment including early PEG
placement, he died one year after the diagnosis of ALS and two
years after the first symptoms of FTD.
Results: Pathological examinations revealed aspiration
pneumonia as cause of death. Besides a predominant
frontotemporal atrophy of the cortex, pathological features of
ALS including atrophy of lower motor neurons as well as Bunina
bodies were present. Immunohistochemical analysis revealed
widespread TDP-43-positive inclusions in the brain and spinal
cord, while stainings for Tau- and Beta-Amyloid rendered
negative results. Thus, the pathological diagnosis of FTLD-TDP
(subtype 2) was made.
Conclusion: This case highlights the common pathological
cause of FTLD and ALS at least in a subgroup of patients.
Pathological examination of these diseases should include
search for TDP-43 and FUS (Fused in Sarcoma Protein)
pathology. Autopsy of deceased FTLD or ALS patients is helpful
in our understanding of these diseases and should be discussed
with patients and caregivers.